Vai ai contenuti. | Spostati sulla navigazione | Spostati sulla ricerca | Vai al menu | Contatti | Accessibilità

| Crea un account

Poloni, Giulia (2016) Arrhythmogenic Cardiomyopathy: identification of novel genes encoding for intercalated disc proteins by next-generation sequencing. [Tesi di dottorato]

Full text disponibile come:

[img]Documento PDF
Tesi non accessible fino a 31 Gennaio 2019 per motivi correlati alla proprietà intellettuale.
Visibile a: nessuno


Abstract (inglese)

Introduction. Arrhythmogenic cardiomyopathy (ACM) is a predominantly genetically determined disease characterized by fibrofatty replacement which leads to right ventricular failure, arrhythmias, and sudden cardiac death (SCD). ACM is inherited as an autosomal dominant trait with incomplete penetrance. Advances in genetic technology have revealed substantial genetic heterogeneity: at least 15 independent loci and 13 disease genes have now been identified associated with the disease, with the large involvement of the genes encoding for desmosomal and area composita proteins. Since causative mutations in ACM genes have been detected in about 60% of probands, additional and still unknown disease-genes could be involved.
Aim of the study. This study aimed at detecting causative mutations underlying the disease expression in a cohort of 59 Italian unrelated index cases through a new targeted next generation sequencing (NGS) approach. Moreover, the identification of novel disease loci and genes in four families with recurrence of ACM was attempted by integrating different genetic approaches.
Methods. Three different NGS approaches have been applied: targeted gene panels (TGP), whole exome sequencing (WES), and whole genome sequencing (WGS). Two custom targeted gene panels, including 56 genes associated with different cardiomyopathies or 69 known and candidate ACM genes have been used to screen both familial and sporadic cases. Genetic analysis was extended to available family members to evaluate the segregation of each mutation identified in the index case. The whole exome of 11 subjects belonging to 4 families was sequenced. In one of these families (Family#6) also WGS in 3 subjects in addition to multipoint linkage analysis was performed.
Results. Targeted gene panels resulted a valuable tool for mutation screening in patients affected with ACM. At least a mutation was found in 15 out of 19 probands screened with the ‘Cardiomyopathies gene panel’. Moreover, by using the ‘ACM known and candidate genes panel’, a mutation in a candidate gene has been identified in 40.6% of probands negative for mutations in known-disease genes. Two novel missense variants in TJP1 gene (p.R265W, p.Y669C), encoding for protein ZO-1 and two in CDH2 gene (p.E493G, p.V491G), encoding for N-cadherin resulted of particular interest, other than a stop mutation in TP63 gene (p.R266*). Both TJP1 mutations affected highly conserved amino acid residues and in silico analysis of p.Y669C mutation, which segregates within the proband’s family, showed its predicted damaging effect into the protein structure.
WES analysis allowed to identify a pathogenic mutation in DSP gene (p.Q1297*) not previously detected by dHPLC in Family#3, and two putative TTN mutations (p.R32573C and p.L32198M) that segregate in Family#4 and Family#5. In Family#5, a rare stop mutation in a candidate gene (CMYA5, p.K3597*) was also identified.
In Family #6, a multi-step approach was applied. The availability of many affected and unaffected family members allowed to perform linkage analysis in an ‘affected only’ approach. The analysis pointed out the presence of two regions with positive pLOD score values on chromosome 19p13.3 and 11q21. The first corresponded to a 7cM region and was shared by all the affected subjects, but one. The 3cM region on chromosome 11q21 segregated in all the affected subjects exception made for two, who carried a PKP2 splice site variant (c.2578-3 T>C). WES performed in 4 patients of the family failed to identified a possible shared pathogenic mutation neither inside the critical regions, nor in the whole exome. These results were confirmed with WGS performed in 2 affected and a healthy individual. Moreover WGS pointed out the presence of a huge amount of complex variants located in repetitive intronic or intragenic regions.
Discussion. The identification of disease-causing mutations facilitates timely diagnosis, allows the prevention of complications and determines the potential risk in close relatives of a proband. For hereditary cardiomyopathies, as well as for most mendelian diseases, in the last ten years NGS technology improved this process allowing to parallel sequence a large amount of genes in a time and cost-efficient manner. Since mutations in the most index cases sequenced by using a targeted gene panel have been detected, it resulted a valid approach not only for genetic testing but also to identify putative novel disease genes. In the present study, novel mutations in genes encoding for intercalated disc proteins (TJP1, CDH2) have been identified, confirming the idea that ACM has to be considered a ‘junctional disease’ rather than only a ‘desmosomal disease’.
Despite TGP remains the most commonly used approach for hereditary cardiomyopathies, WES, applied in familial ACM cases, allowed to identify novel variants in candidate genes that would be not detected with TGP and could have a possible pathogenic role or a modifier effect in the phenotypic expression. Finally, even though WGS didn’t allow to make a genotype-phenotype correlation in Family #6, the huge amount of data produced represent permanent data that could be re-analysed in the future with new insights and the discovery of novel disease genes.

Abstract (italiano)

Introduzione. La cardiomiopatia aritmogena (ACM) è una patologia ereditaria del muscolo cardiaco, caratterizzata da una progressiva sostituzione adiposa o fibroadiposa a carico prevalentemente del miocardio del ventricolo destro. Dal punto di vista clinico, è una patologia eterogenea con ampia variabilità clinica inter- ed intra- familiare; presenta infatti sia forme completamente asintomatiche sia forme molto gravi con rischio di morte improvvisa. Questa patologia, geneticamente eterogenea, è trasmessa come carattere autosomico dominante a penetranza incompleta ed espressività variabile. Ad oggi 15 loci e 13 geni sono stati associati alla malattia, di cui gran parte codificano per proteine desmosomali e proteine della cosiddetta area composita dei dischi intercalari. Poiché sono state identificate mutazioni causative in geni noti sono nel 60% dei casi, altri geni, non ancora identificati, potrebbero essere coinvolti nella comparsa del fenotipo patologico.
Scopo della ricerca. Nello studio descritto nella presente tesi, il DNA di 59 casi indice è stato analizzato attraverso due diversi pannelli di geni tramite sequenziamento di nuova generazione (NGS). Inoltre, in quattro famiglie con ricorrenza di casi di ACM, in cui non sono state identificate mutazioni nei geni desmosomali, sono state integrate diverse tecniche allo scopo di identificare nuovi loci e geni malattia.
Metodi. Nell’ambito del sequenziamento di nuova generazione (NGS) tre diversi approcci sono stati utilizzati: il sequenziamento di pannelli di geni target (TGP), il sequenziamento dell’intero esoma (WES) e il sequenziamento dell’intero genoma. Due sono i pannelli di geni considerati, uno comprendente 56 geni associati a diverse cardiomiopatie, l’altro comprendente 69 geni, tra cui i 13 geni associati alla cariomiopatia aritmogena e 56 geni candidati. L’analisi genetica è stata poi estesa ai familiari dei probandi, ove disponibili, per valutare la segregazione delle mutazioni identificate. L’intero esoma è stato poi sequenziato in 11 soggetti appartenenti a 4 diverse famiglie. Infine, in una di queste famiglie (Famiglia#6) è stata eseguita un’analisi di linkage ed è stato sequenziato l’intero genoma di tre soggetti.
Risultati. L’utilizzo dei pannelli di geni target si è rivelato una buona strategia per lo screening di mutazioni in pazienti affetti da ACM: almeno una mutazione è stata trovata in 15 probandi su un totale di 19 analizzati con il pannello di geni associati a diverse cardiomiopatie; inoltre, è stata identificata una mutazione in uno dei geni candidati nel 40.6% dei probandi sequenziati con il secondo pannello e risultati negativi per mutazioni nei geni noti. Tra queste mutazioni, risultano di particolare interesse 2 nuove mutazioni missenso localizzate nel gene TJP1 (p.R265W, p.Y669C), 2 mutazioni nel gene che codifica per l’N-caderina (CDH2, p.E493G, p.V491G) e una mutazione di stop nel gene TP63 (p.R266*). Entrambe le mutazioni di TJP1 riguardano aminoacidi altamente conservati, inoltre un’analisi in silico degli effetti della mutazione p.Y669C, che segrega all’interno della famiglia, evidenzia un riarrangiamento della struttura proteica della proteina che riporta la mutazione rispetto alla proteina wild-type.
L’analisi dell’esoma nella Famiglia#3 ha permesso di identificare una mutazione patogena di stop nel gene DSP, che non era stato possibile individuare al precedente screening tramite dHPLC. Inoltre, tale approccio ha permesso di identificare due putative mutazioni nel gene TTN (p.R32573C and p.L32198M) che segregano nelle Famiglie #4 e #5, rispettivamente. Nella Famiglia #5 inoltre è stata identificata una rara mutazione di stop in un gene candidato (CMYA5, p.K3597*). Per lo studio della Famiglia#6, invece, sono stati utilizzati diversi approcci. Data la disponibilità di molti soggetti affetti e sani appartenenti alla famiglia, in seguito alla genotipizzazione degli stessi, è stata eseguita un’analisi di linkage. L’analisi ha evidenziato la presenza di due loci che riportano valori di lod score positivi a livello del cromosoma 19p13.3 e del cromosoma 11q21. Il primo locus corrisponde ad una regione di 7 cM ed è condiviso da tutti i soggetti affetti della famiglia, eccetto uno. La regione di 3cM nel cromosoma 11q21 invece segrega in tutti i soggetti affetti ad eccezione di due, che portano una mutazione in un sito di splicing del gene PKP2 (c.2578-3 T>C). Il sequenziamento dell’esoma in 4 soggetti affetti della famiglia non ha permesso di identificare nuove mutazioni condivise né all’interno delle due regioni critiche, né all’interno dell’intero esoma. Tali risultati sono stati confermati dal sequenziamento del genoma effettuato in due affetti e un soggetto sano della famiglia. Il sequenziamento del genoma ha inoltre messo in luce la presenza di un’enorme quantità di varianti complesse localizzate in regioni introniche o intrageniche.
Discussione. L’identificazione di mutazioni causative nella cardiomiopatia aritmogena facilita la diagnosi tempestiva, permette di prevenire eventuali complicazioni e determina il rischio di sviluppare la malattia nei familiari di un soggetto affetto. Per le cardiomiopatie ereditarie, come per la maggior parte delle malattie mendeliane, negli ultimi 10 anni le tecniche NGS hanno apportato grossi miglioramenti nel processo di identificazione di mutazioni, permettendo di sequenziare una grande quantità di geni parallelamente, in modo più rapido e meno costoso. In questo studio, dal momento che sono state identificate mutazioni nella maggior parte di probandi analizzati, l’utilizzo di pannelli di geni target si è dimostrato un valido approccio non solo per un test genetico ma anche per l’identificazione di nuovi geni malattia. Sono state infatti identificate nuove mutazioni in geni che codificano per proteine dei dischi intercalari dei cardiomiociti, confermando l’idea che l’ACM deve essere considerata una ‘malattia delle giunzioni’ piuttosto che una ‘malattia dei desmosomi’.
Nonostante l’utilizzo di pannelli di geni target rimanga l’approccio più comunemente usato nella ricerca di mutazioni nelle cardiomiopatie ereditarie, il sequenziamento dell’intero esoma, applicato in questo studio solo a casi familiari, ha permesso di identificare varianti in geni candidati non inclusi nei pannelli di geni e che potrebbero avere un ruolo nell'espressione del fenotipo patologico. Infine, nonostante il sequenziamento del genoma nella Famiglia#6 non abbia permesso al momento di stabilire una correlazione tra genotipo e fenotipo al momento, la mole di dati prodotti potrà essere rianalizzata in futuro alla luce di nuovi geni annotati e nuovi geni malattia identificati.

Aggiungi a RefWorks
Tipo di EPrint:Tesi di dottorato
Relatore:Rampazzo, Alessandra
Data di deposito della tesi:29 Gennaio 2016
Anno di Pubblicazione:31 Gennaio 2016
Parole chiave (italiano / inglese):cardiomiopatia/cardiomyopathy; morte improvvisa/sudden death; sequenziamento di nuova generazione/next generation sequencing; genetica molecolare/molecular genetics; dischi intercalari/intercalated discs
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/18 Genetica
Struttura di riferimento:Dipartimenti > Dipartimento di Biologia
Codice ID:9054
Depositato il:21 Ott 2016 15:46
Simple Metadata
Full Metadata
EndNote Format


I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

Adessi C, Matton G, Ayala G, et al. Solid phase DNA amplification: characterisation of primer attachment and amplification mechanisms. Nucleic Acids Res. 2000; 28(20):E87. Cerca con Google

Ai D, Fu X, Wang J, et al. Canonical Wnt signaling functions in second heart field to promote right ventricular growth. Proc Natl Acad Sci USA. 2007; 104(22):9319-24. Cerca con Google

Alcalai R, Metzger S, Rosenheck S, Meiner V, Chajek-Shaul T. A recessive mutation in desmoplakin causes arrhythmogenic right ventricular dysplasia, skin disorder, and woolly hair. J Am Coll Cardiol. 2003; 42(2):319-27. Cerca con Google

Alimperti S and Andreadis ST. CDH2 and CDH11 act as regulators of stem cell fate decisions. Stem Cell Research. 2015; 14(3):270-82. Cerca con Google

Anderson, J. M. Cell signalling: MAGUK magic. Curr. Biol. 1996; 6(4):382-4. Cerca con Google

Angst BD, Nilles LA, Green KJ. Desmoplakin II expression is not restricted to stratified epithelia. J Cell Sci. 1990; 97(2):247–57. Cerca con Google

Asano Y, Takashima S, Asakura M, et al. Lamr1 functional retroposon causes right ventricular dysplasia in mice. Nature genetics. 2004; 36(2):123-130. Cerca con Google

Asimaki A, Syrris P, Wichter T, Matthias P, Saffitz JE, McKenna WJ. A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet. 2007; 81(5):964-73. Cerca con Google

Asimaki A, Tandri H, Huang H, et al. A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy. N Engl J Med. 2009; 360(11):1075-84. Cerca con Google

Asimaki A, Kléber AG, MacRae CA, Saffitz JE. Arrhythmogenic Cardiomyopathy - New Insights into Disease Mechanisms and Drug Discovery. Prog Pediatr Cardiol. 2014; 37(1-2):3-7. Cerca con Google

Aylon Y and Oren M. New plays in the p53 theater. Curr Opin Genet Dev. 2011; 21(1):86-92. Cerca con Google

Awad MM, Dalal D, Tichnell C, et al. Recessive arrhythmogenic right ventricular dysplasia due to novel cryptic splice mutation in PKP2. Human Mutat. 2006; 27(11):1157. Cerca con Google

Azaouagh A, Churzidse S, Konorza T, Erbel R. Arrhythmogenic right ventricular cardiomyopathy/dysplasia: A review and update. Clin Res Cardiol. 2011; 100(5):383-94. Cerca con Google

Bagattin A, Veronese C, Bauce B, et al. Denaturing HPLC-based approach for detecting RYR2 mutations involved in malignant arrhythmias. Clin Chem. 2004; 50(7):1148-55. Cerca con Google

Bailey-Wilson JE and Wilson AF. Linkage Analysis in the Next-Generation Sequencing Era. Hum Hered. 2011; 72(4):228-36. Cerca con Google

Barker RJ, Price RL, Gourdie RG. Increased association of ZO-1 with connexin43 during remodeling of cardiac gap junctions. Circ Res. 2002; 90(3):317–24. Cerca con Google

Basso C, Thiene G, Corrado D, Angelini A, Nava A, Valente M. Arrhythmogenic right ventricular cardiomyopathy. Dysplasia, dystrophy, or myocarditis? Circulation. 1996; 94(5):983-91. Cerca con Google

Basso C, Fox PR, Meurs KM, et al. Arrhythmogenic right ventricular cardiomyopathy causing sudden cardiac death in boxer dogs: a new animal model of human disease. Circulation. 2004; 109(9):1180-5. Cerca con Google

Basso C and Thiene G. Adipositas cordis, fatty infiltration of the right ventricle, and arrhythmogenic right ventricular cardiomyopathy. Just a matter of fat? Cardiovasc Pathol. 2005; 14(1):37-41. Cerca con Google

Basso C, Czarnowska E, Della Barbera M, et al. Ultrastructural evidence of intercalated disc remodelling in arrhythmogenic right ventricular cardiomyopathy: an electron microscopy investigation on endomyocardial biopsies. Eur Heart J. 2006; 27(15):1847-54. Cerca con Google

Basso C and Thiene G. Autopsy and endomyocardial biopsy findings. In: Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia. Marcus FI, Nava A, Thiene G, editors. Milan, Italy Springer Verlag; 2007: pp. 29-44. Cerca con Google

Basso C, Corrado D, Marcus FI, Nava A, Thiene G. Arrhythmogenic right ventricular cardiomyopathy. Lancet. 2009; 373(9671):1289-300. Cerca con Google

Bauce B, Frigo G, Marcus FI, et al. Comparison of clinical features of arrhythmogenic right ventricular cardiomyopathy in men versus women. Am J Cardiol. 2008; 102(9):1252-7. Cerca con Google

Bauce B, Nava A, Beffagna G, et al. Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Heart Rhythm. 2010; 7(1):22-29. Cerca con Google

Beffagna G, Occhi G, Nava A, et al. Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Cardiovasc Res. 2005; 65(2):366-73. Cerca con Google

Beffagna G, De Bortoli M, Nava A, et al. Missense mutations in desmocollin-2 N-terminus, associated with arrhythmogenic right ventricular cardiomyopathy, affect intracellular localization of desmocollin-2 in vitro. BMC Med Genet. 2007; 8:65. Cerca con Google

Bennet PM, Maggs AM, Baines AJ, Pinder JC. The Transitional Junction: A New Functional Subcellular Domain at the Intercalated Disc. Molecular Biology of the Cell. 2006; 17(4):2091-100. Cerca con Google

Benson MA, Tinsley CL, Blake DJ. Myospryn is a novel binding partner for dysbindin in muscle. J Biol Chem. 2004; 279(11):10450-8. Cerca con Google

Ben-Yosef T and Francomano CA. Characterization of the human talin (TLN) gene: genomic structure, chromosomal localization, and expression pattern. Genomics. 1999; 62(2):316-9. Cerca con Google

Ben-Ze'ev A and Geiger B. Differential molecular interactions of beta-catenin and plakoglobin in adhesion, signaling and cancer. Curr Opin Cell Biol. 1998; 10(5):629-39. Cerca con Google

Bhonsale A, Groeneweg JA, James CA, et al. Impact of genotype on clinical course in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated mutation carriers. Eur Heart J. 2015; 36(14):847-55. Cerca con Google

Bierkamp C, Mclaughlin KJ, Schwarz H, Huber O, Kemler R. Embryonic heart and skin defects in Cerca con Google

mice lacking plakoglobin. Dev Biol. 1996; 180(2):780-5. Cerca con Google

Biswas A, Rao VR, Seth S, Maulik SK. Next generation sequencing in cardiomyopathy: towards personalized genomics and medicine. Mol Biol Rep. 2014; 41(8):4881-8. Cerca con Google

Bonne G, Di Barletta MR, Varnous S, et al. Mutations in the gene encoding lamin A/C cause auto- somal dominant Emery-Dreifuss muscular dystrophy. Nat Genet. 1999; 21(3):285-8. Cerca con Google

Borrmann CM, Grund C, Kuhn C, Hofmann I, Pieperhoff S, Franke WW. The area composita of adhering junctions connecting heart muscle cells of vertebrates. II. Colocalizations of desmosomal and fascia adhaerens molecules in the intercalated disk. Eur J Cell Biol. 2006; 85(6):469-85. Cerca con Google

Bowles NE, Ni J, Marcus F, Towbin JA. The detection of cardiotropic viruses in the myocardium of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol. 2002; 39(5):892-95. Cerca con Google

Bruce AF, Rothery S, Dupont E, Severs NJ. Gap junction remodelling in human heart failure is associated with increased interaction of connexin43 with ZO-1. Cardiovasc Res. 2008; 77(4):757-65. Cerca con Google

Brun F, Barnes C V, Sinagra G, et al. Titin and desmosomal genes in the natural history of arrhythmogenic right ventricular cardiomyopathy. J Med Genet. 2014; 51(10):669-76. Cerca con Google

Burridge K and Mangeat P. An interaction between vinculin and talin. Nature. 1984; 308(5961):744-6. Cerca con Google

Calabrese F, Basso C, Carturan E, Valente M, Thiene G. Arrhythmogenic right ventricular cardiomyopathy/dysplasia: is there a role for viruses? Cardiovasc Pathol. 2006; 15(1):11-17. Cerca con Google

Calore M, Lorenzon A, De Bortoli M, Poloni G, Rampazzo A. Arrhythmogenic cardiomyopathy: a disease of intercalated discs. Cell Tissue Res. 2015; 360(3):491-500. Cerca con Google

Caspi O, Huber I, Gepstein A, et al. Modeling of Arrhythmogenic Right Ventricular Cardiomyopathy With Human Induced Pluripotent Stem Cells. Circ Cardiovasc Genet. 2013; 6(6):557-68. Cerca con Google

Cenni V, Sabatelli P, Mattioli E, et al. Lamin A N-terminal phosphorylation is associated with myoblast activation: impairment in Emery-Dreifuss muscular dystrophy. J Med Genet. 2005; 42(3):214-20. Cerca con Google

Cerrone M, Noorman M, Lin X, et al. Sodium current deficit and arrhythmogenesis in a murine model of plakophilin-2 haploinsufficiency. Cardiovasc Res. 2012; 95(4):460-8. Cerca con Google

Chauveau C, Rowell J, Ferreiro A. A rising titan: TTN review and mutation update. Hum Mutat. 2014; 35(9):1046-59. Cerca con Google

Chen SN, Gurha P, Lombardi R, Ruggiero A, Willerson JT, Marian a. J. The hippo pathway is activated and is a causal mechanism for adipogenesis in arrhythmogenic cardiomyopathy. Circ Res. 2014; 114(3):454-68. Cerca con Google

Chen X, Bonne S, Hatzfeld M, van Roy F, Green KJ. Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta-catenin signaling. J Biol Chem. 2002; 277(12):10512-22. Cerca con Google

Christensen AH, Benn M, Tybjaerg-Hansen A, Haunso S, Svendsen JH. Missense variants in plakophilin-2 in arrhythmogenic right ventricular cardiomyopathy patients-disease-causing or innocent bystanders? Cardiology. 2010; 115(2):148-54. Cerca con Google

Christensen AH, Andersen CB, Tybjaerg-Hansen A, Haunso S, Svendsen JH. Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy. Clin Genet. 2011; 80(3):256-64. Cerca con Google

Corrado D, Thiene G, Nava A, Rossi L, Pennelli N. Sudden death in young competitive athletes: Clinicopathologic correlations in 22 cases. Am J Med. 1990; 89(5):588-96. Cerca con Google

Corrado D, Basso C, Thiene G, et al. Spectrum of clinicopathologic manifestations arrhythmogenic right ventricular cardiomyopathy / dysplasia: a multicenter study. J Am Coll Cardiol. 1997; 30(6):1512-20. Cerca con Google

Corrado D, Leoni L, Link MS, et al. Implantable cardioverter-defibrillator therapy for prevention of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia. Circulation. 2003; 108(25):3084-91. Cerca con Google

Corrado D, Basso C, Leoni L, et al. Three-dimensional electroanatomic voltage mapping increases accuracy of diagnosing arrhythmogenic right ventricular cardiomyopathy/dysplasia. Circulation. 2005; 111(23):3042-50. Cerca con Google

Cox MG, van der Smagt JJ, Noorman M, et al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy diagnostic task force criteria: impact of new task force criteria. Circ Arrhythm Electrophysiol. 2010; 3(2):126-33. Cerca con Google

Dalal D, Nasir K, Bomma C et al. Arrhythmogenic right ventricular dysplasia: A United States experience. Circulation. 2005; 112(25):3823-32. Cerca con Google

Dalal D, Molin LH, Piccini J, et al. Clinical features of arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in plakophilin-2. Circulation. 2006; 113(13):1641-9. Cerca con Google

Daliento L, Turrini P, Nava A, et al. Arrhythmogenic right ventricular cardiomyopathy in young versus adult patients: similarities and differences. J Am Coll Cardiol. 1995; 25(3):655-64. Cerca con Google

d'Amati G, Bagattin A, Bauce B, et al. Juvenile sudden death in a family with polymorphic ventricular arrhythmias caused by a novel RYR2 gene mutation: Evidence of specific morphological substrates. Hum Pathol. 2005; 36(7):761-7. Cerca con Google

Delmar M, Coombs W, Sorgen P, Duffy HS, Taffet SM. Structural bases for the chemical regulation of Connexin43 channels. Cardiovasc Res. 2004; 62(2):268-75. Cerca con Google

Delmar M. The intercalated disk as a single functional unit. Heart Rhythm. 2004;1(1):12-13. Cerca con Google

Delmar M and Sorgen PL. Molecular organization and regulation of the cardiac gap junction channel Connexin43. 2009. In: Zipes DP, Jalife J (eds) Cardiac electrophysiology: from cell to bedside. Saunders Elsevier, Philadelphia, pp 85–92. Cerca con Google

Delmar M and McKenna WJ. The cardiac desmosome and arrhythmogenic cardiomyopathies: From gene to disease. Circ Res. 2010; 107(6):700-14. Cerca con Google

den Haan AD, Tan BY, Zikusoka MN, et al. Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Cardiovasc Genet. 2009; 2(5):428-35. Cerca con Google

Diekstra A, Bosgoed E, Rikken A, et al. Translating sanger-based routine DNA diagnostics into generic massive parallel ion semiconductor sequencing. Clin Chem. 2015; 61(1):154-62. Cerca con Google

Di Resta C, Pietrelli A, Sala S, et al. High-throughput genetic characterization of a cohort of Brugada syndrome patients. Hum Mol Genet. 2015; 24(20):5828-35. Cerca con Google

Dusek RL, Godsel LM, Green KJ. Discriminating roles of desmosomal cadherins: Beyond desmosomal adhesion. J Derm Science. 2007; 45(1):7-21. Cerca con Google

Elliott P, Andersson B, Arbustini E, et al. Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2008; 29(2):270-6. Cerca con Google

Elliott P, O'Mahony C, Syrris P, et al. Prevalence of desmosomal protein gene mutations in patients with dilated cardiomyopathy. Circ Cardiovasc Genet. 2010; 3(4):314-22. Cerca con Google

Ellis LA, Taylor CF, Taylor GR. A comparison of fluorescent SSCP and denaturing HPLC for high throughput mutation scanning. Hum Mutat. 2000; 15(6):556-64. Cerca con Google

Eshkind L, Tian Q, Schmidt A, Franke WW, Windoffer R, Leube RE. Loss of desmoglein 2 suggests essential functions for early embryonic development and proliferation of embryonal stem Cerca con Google

cells. Eur J Cell Biol. 2002; 81(11):592-8. Cerca con Google

Fatkin D, MacRae C, Sasaki T, et al. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction- system disease. N Engl J Med. 1999; 341(23):1715-24. Cerca con Google

Fedurco M, Romieu A, Williams S, Lawrence I, Turcatti G. BTA, a novel reagent for DNA attachment on glass and efficient generation of solid-phase amplified DNA colonies. Nucleic Acids Res. 2006; 34(3):e22. Cerca con Google

Fontaine G, Frank R, Guiraudon G, et al. Signification des troubles de conduction intraventriculaire observes dans la dysplasia ventriculaire droite arhythmogene. Arc Mal Coeur. 1984; 77:872-9. Cerca con Google

Forbes MS and Sperelakis N. Intercalated discs of mammalian heart: a review of structure and function. Tissue Cell. 1985; 17(5):605-48. Cerca con Google

Fox PR, Maron BJ, Basso C, Liu S, Thiene G. Spontaneously occurring arrhythmogenic right ventricular cardiomyopathy in the domestic cat. A new animal model similar to the human disease. Circulation. 2000; 102(15):1863-70. Cerca con Google

Franke WW, Borrmann CM, Grund C, Pieperhoff S. The area composita of adhering junctions connecting heart muscle cells of vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by immunoelectron microscopy of desmosomal proteins. Eur J Cell Biol. 2006; 85(2):69-82. Cerca con Google

Franke WW, Dörflinger Y, Kuhn C, et al. Protein LUMA is a cytoplasmic plaque constituent of various epithelial adherens junctions and composite junctions of myocardial intercalated disks: A unifying finding for cell biology and cardiology. Cell Tissue Res. 2014; 357(1):159-72. Cerca con Google

Fressart V, Duthoit G, Donal E, et al. Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice. Europace. 2010; 12(6):861-8. Cerca con Google

Fϋrst DO, Osborn M, Nave R, Weber K. The organization of titin filaments in the half-sarcomere revealed by monoclonal antibodies in immunoelectron microscopy: a map of ten nonrepetitive epitopes starting at the Z line extends close to the M line. J Cell Biol. 1988; 106(5):1563-72. Cerca con Google

Gallicano GI, Kouklis P, Bauer C, et al. Desmoplakin is required early in development for assembly of desmosomes and cytoskeletal linkage. J Cell Biol. 1998; 143(2):2009-22. Cerca con Google

Gallicano GI, Bauer C, Fuchs E. Rescuing desmoplakin function in extra-embryonic ectoderm reveals the importance of this protein in embryonic heart, neuroepithelium, skin, and vasculature. Development. 2001; 128(6):929-41. Cerca con Google

Garcia-gras E, Lombardi R, Giocondo MJ, et al. Suppression of canonical Wnt/beta-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhytmogenic right ventricular cardiomyopathy. J Clin Invest. 2006; 116(7):2012-21. Cerca con Google

Garrod D, Chidgey M. Desmosome structure, composition and function. Biochim Biophys Acta. 2008; 1778(3):572-87. Cerca con Google

Gerull B, Gramlich M, Atherton J, et al. Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy. Nat Genet. 2002; 30(2):201-4. Cerca con Google

Gerull B, Heuser A, Wichter T, et al. Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet. 2004; 36(11):1162-4. Cerca con Google

Gerull B, Atherton J, Geupel A, et al. Identification of a novel frameshift mutation in the giant muscle filament titin in a large Australian family with dilated cardiomyopathy. J Mol Med. 2006; 84(6):478-83. Cerca con Google

Gilissen C, Hoischen A, Brunner HG, Veltman J A. Disease gene identification strategies for exome sequencing. Eur J Hum Genet. 2012; 20(5):490-7. Cerca con Google

Gilissen C, Hehir-Kwa JY, Thung DT, et al. Genome sequencing identifies major causes of severe intellectual disability. Nature. 2014; 511(7509):344-7. Cerca con Google

Golbus JR, Puckelwartz MJ, Fahrenbach JP, et al. Population-Based Variation in Cardiomyopathy Genes. Circ Cardiovasc Genet. 2012; 5(4):391-9. Cerca con Google

Gomes J, Finlay M, Ahmed AK, et al. Electrophysiological abnormalities precede overt structural changes in arrhythmogenic right ventricular cardiomyopathy due to mutations in desmoplakin-A combined murine and human study. Eur Heart J. 2012; 33(15):1942-53. Cerca con Google

Goossens S, Janssens B, Bonne S, et al. A unique and specific interaction between alphaT-catenin and plakophilin-2 in the area composita, the mixedtype junctional structure of cardiac intercalated discs. J Cell Sci. 2007; 120(12):2126-36. Cerca con Google

Groeneweg JA, Bhonsale A, James CA, et al. Clinical Presentation, Long-Term Follow-Up, and Outcomes of 1001 Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Patients and Family Members. Circ Cardiovasc Genet. 2015; 8(3):437-46. Cerca con Google

Grossmann KS, Grund C, Huelsken J, et al. Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation. J Cell Biol. 2004; 167(1):149-60. Cerca con Google

Gunderson KL, Steemers FJ, Lee G, Mendoza LG, Chee MS. A genome-wide scalable SNP genotyping assay using microarray technology. Nat Genet. 2005; 37(5):549-54. Cerca con Google

Haghighi K, Kolokathis F, Gramolini AO, et al. A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy. Proc Natl Acad Sci U S A. 2006; 103(5):1388-93. Cerca con Google

Hamid MS, Norman M, Quraishi A, et al. Prospective evaluation of relatives for familial arrhythmogenic right ventricular cardiomyopathy/dysplasia reveals a need to broaden diagnostic criteria. J Am Coll Cardiol. 2002; 40(8):1445-50. Cerca con Google

Hatzfeld M. Plakophilins: Multifunctional proteins or just regulators of desmosomal adhesion? Review. Biocm.Biophys Acta. 2006; 1773(1):69-77. Cerca con Google

Herman DS, Lam L, Taylor MR, et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012; 366(7):619-628. Cerca con Google

Heuser A, Plovie ER, Ellinor PT, et al. Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet. 2006; 79(6):1081-8. Cerca con Google

Hulot JS, Jouven X, Empana JP, Frank R, Fontaine G. Natural history and risk stratification of Cerca con Google

arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation. 2004; 110(14):1879-84. Cerca con Google

Hunter AW, Barker RJ, Zhu C, Gourdie RG. Zonula occludens-1 alters connexin43 gap junction size and organization by influencing channel accretion. Mol Biol Cell. 2005; 16(12): 5686–98. Cerca con Google

Ihrie RA, Marques MR, Nguyen BT, et al. Perp is a p63-regulated gene essential for epithelial integrity. Cell. 2005; 120(6):843-856. Cerca con Google

Itoh-Satoh M, Hayashi T, Nishi H, et al. Titin mutations as the molecular basis for dilated cardiomyopathy. Biochem Biophys Res Commun. 2002; 291(2):385-393. Cerca con Google

Jonkman MF, Pasmooij AM, Pasmans SG, et al. Loss of desmoplakin tail causes lethal acantholytic epidermolysis bullosa. Am J Hum Genet. 2005; 77(4):653-60. Cerca con Google

Kannankeril PJ, Mitchell BM, Goonasekera SA, et al. Mice with the R176Q cardiac ryanodine receptor mutation catecholamine induced ventricular tachycardia and cardiomyopathy. Proc Natl Acad Sci U S A. 2006; 103(32):12179-84. Cerca con Google

Kant S, Krusche C, Gaertner A, Milting H, Leube RE. Loss of plakoglobin immunoreactivity in intercalated discs in arrhythmogenic right ventricular cardiomyopathy: Protein mislocalization versus epitope masking. Cardiovasc Res. 2016; 109(2):260-71. Cerca con Google

Kaplan SR, Gard JJ, Carvajal-Huerta L, Ruiz-Cabezas JC, Thiene G, Saffitz JE. Structural and molecular pathology of the heart in Carvajal syndrome. Cardiovasc Pathol. 2004a; 13(1):26-32. Cerca con Google

Kaplan SR, Gard JJ, Protonotarios N, et al. Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease). Heart Rhythm. 2004b; 1(1):3-11. Cerca con Google

Kapoun AM, Liang F, O’Young G, et al. B-type natriuretic peptide exerts broad functional opposition to transforming growth factor-beta in primary human cardiac fibroblasts: fibrosis, myofibroblast conversion, proliferation, and inflammation. Circ Res. 2004; 94(4):453-61. Cerca con Google

Kim C, Wong J, Wen J, et al. Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs. Nature. 2013; 494(7435):105-10. Cerca con Google

Kirchhof P, Fabritz L, Zwiener M, et al. Age- and training-dependent development of arrhythmogenic right ventricular cardiomyopathy in heterozygous plakoglobin-deficient mice. Circulation. 2006; 114(17):1799-806. Cerca con Google

Klauke B, Kossmann S, Gaertner A, et al. De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy. Hum Mol Genet. 2010; 19(23):4595-4607. Cerca con Google

Klymkowsky MW, Williams BO, Barish GD, Varmus HE, Vourgourakis YE. Membrane-anchored plakoglobins have multiple mechanisms of action in Wnt signaling. Mol Biol Cell. 1999; 10(10):3151-69. Cerca con Google

Kostetskii I, Li J, Xiong Y, et al. Induced deletion of the N-cadherin gene in the heart leads to dissolution of the intercalated disc structure. Circ Res. 2005; 96(3):346-54. Cerca con Google

Kouloumenta A, Mavroidis M, Capetanaki Y. Proper perinuclear localization of the TRIM-like protein myospryn requires its binding partner desmin. J Biol Chem. 2007; 282(48):35211-21. Cerca con Google

Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES. Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet. 1996; 58(6):1347-63. Cerca con Google

Krusche CA, Holthofer B, Hofe V, et al. Desmoglein 2 mutant mice develop cardiac fibrosis and dilation. Basic Res Cardiol. 2011; 106(4):617-33. Cerca con Google

Lacroix D, Lions C, Klug D, Prat A. Arrhythmogenic right ventricular dysplasia: catheter ablation, MRI, and heart trans- plantation. J Cardiovasc Electrophysiol. 2005; 16(2):235-6. Cerca con Google

Lahtinen AM, Lehtonen A, Kaartinen M, et al. Plakophilin-2 missense mutations in arrhythmogenic right ventricular cardiomyopathy. Int J Cardiol. 2008; 126(1):92-100. Cerca con Google

Laing JG, Saffitz JE, Steinberg TH, Yamada KA. Diminished zonula occludens-1 expression in the failing human heart. Cardiovascular Pathology. 2007; 16(3):159-64. Cerca con Google

Lakdawala NK, Dellefave L, Redwood CS, et al. Familial dilated cardiomyopathy caused by an alpha-tropomyosin mutation: the distinctive natural history of sarcomeric dilated cardiomyopathy. J Am Coll Cardiol. 2010; 55(4):320-9. Cerca con Google

Lammerding J, Schulze PC, Takahashi T, et al. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J Clin Invest. 2004; 113(3):370-8. Cerca con Google

Landstrom AP, Parvatiyar MS, Pinto JR, et al. Molecular and functional characterization of novel hypertrophic cardiomyopathy susceptibility mutations in TNNC1-encoded troponin C. J Mol Cell Cardiol. 2008; 45(2):281-8. Cerca con Google

Lelieveld SH, Spielmann M, Mundlos S, Veltman J a., Gilissen C. Comparison of Exome and Genome Sequencing Technologies for the Complete Capture of Protein-Coding Regions. Hum Mutat. 2015; 36(8):815-22. Cerca con Google

LeWinter MM and Granzier H. Cardiac Titin - A Multifunctional Giant. Circulation. 2010; 121(19):2137-45. Cerca con Google

Li D, Liu Y, Maruyama M, et al. Restrictive loss of plakoglobin in cardiomyocytes leads to arrhythmogenic cardiomyopathy. Hum Mol Genet. 2011; 20(23):4582-96. Cerca con Google

Li J, Patel VV, Kostetskii I, et al. Cardiac-Specific Loss of N-Cadherin Leads to Alteration in Connexins With Conduction Slowing and Arrhythmogenesis. Circ Res. 2005; 97(5):474-81. Cerca con Google

Li J, Levin MD, Xiong Y, Petrenko N, Patel V V, Radice GL. N-cadherin haploinsufficiency affects cardiac gap junctions and arrhythmic susceptibility. J Mol Cell Cardiol. 2008; 44(3):597-606. Cerca con Google

Li J, Swope D, Raess N, Cheng L, Muller EJ, Radice GL. Cardiac tissue-restricted deletion of plakoglobin results in progressive cardiomyopathy and activation of {beta}-catenin signaling. Mol Cell Biol. 2011; 31(6):1134-44. Cerca con Google

Liang WC, Mitsuhashi H, Keduka E, et al. TMEM43 Mutations in Emery-Dreifuss Muscular Dystrophy-Related Myopathy. Am Neurol Ass. 2011; 69(6):1005-13. Cerca con Google

Lindner TH and Hoffmann K. EasyLINKAGE: a PERL script for easy and automated two-/multi-point linkage analysis. Bioinformatics. 2005; 21(3):405-7. Cerca con Google

Lobo F, Silver MD, Butany J et al. Left ventricular involvement in right ventricular dysplasia/cardiomyopathy. Can J Cardiol. 1999; 15(11):1239-47. Cerca con Google

Lombardi R and Marian AJ. Molecular genetics and pathogenesis of arrhythmogenic right ventricular cardiomyopathy: A disease of cardiac stem cells. Pediatr Cardiol. 2011; 32(3):360-5. Cerca con Google

Lorenzon A, Pilichou K, Rigato I, et al. Homozygous Desmocollin-2 Mutations and Arrhythmogenic Cardiomyopathy. Am J Cardiol. 2015; 116(8):1245-51. Cerca con Google

Luo Y, Radice GL. Cadherin-mediated adhesion is essential for myofibril continuity across the plasma membrane but not for assembly of the contractile apparatus. J Cell Sci,2003; 116(8):1471-9. Cerca con Google

Lye MF, Fanning AS, Su Y, Anderson JM, Lavie A. Insights into Regulated Ligand Binding Sites from the Structure of ZO-1 Src Homology 3-Guanylate Kinase Module. J Biol Chem. 2010; 285(18):13907-17. Cerca con Google

Ma D, Wei H, Lu J, et al. Generation of patient-specific induced pluripotent stem cell-derived cardiomyocytes as a cellular model of arrhythmogenic right ventricular cardiomyopathy. Eur Heart J. 2013; 34(15):1122-33. Cerca con Google

Marcus FI, Fontaine GH, Guiraudon G, et al. Right ventricular dysplasia: a report of 24 adult cases. Circulation. 1982; 65(2):384-98. Cerca con Google

Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia Proposed Modification of the Task Force Criteria. Eur Heart J. 2010; 31(7):806-14. Cerca con Google

Maron BJ, Towbin JA, Thiene G, et al.; American Heart Association; Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translation Biology Interdisiplinary Working Groups, Council on Epidemiology and Prevention. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation. 2006; 113(14):1807-16. Cerca con Google

Martherus R, Jain R, Takagi K, et al. Accelerated cardiac remodeling in desmoplakin transgenic mice in response to endurance exercise is associated with perturbed Wnt/β-catenin signaling. Am J Physiol Heart Circ Physiol. 2016; 310(2):H174-87. Cerca con Google

Martin ED, Moriarty MA, Byrnes L, Grealy M. Plakoglobin has both structural and signalling roles in zebrafish development. Dev Biol. 2009; 327(1):83-96. Cerca con Google

McKenna WJ, Thiene G, Nava A, et al. Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task Force of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the International Society. Br Heart J. 1994; 71(3):215-8. Cerca con Google

McKoy G, Protonotarios N, Crosby A, et al. Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet. 2000; 355(9221):2119-24. Cerca con Google

McLendon PM and Robbins J. Desmin-related cardiomyopathy: an unfolding story. Am J Physiol Heart Circ Physiol. 2011; 301(4):H1220-8. Cerca con Google

Merner ND, Hodgkinson KA, Haywood AF, et al. Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene. Am J Hum Genet. 2008; 82(4):809-21. Cerca con Google

Mertens C, Hofmann I, Wang Z, et al. Nuclear particles containing RNA polymerase III complexes associated with the junctional plaque protein plakophilin 2. Proc Natl Acad Sci USA. 2001; 98(14):7795-800. Cerca con Google

Meurs KM, Ederer MM, Stern JA. Desmosomal gene evaluation in Boxers with arrhythmogenic right ventricular cardiomyopathy. Am J Vet Res. 2007; 68(12):1338-41. Cerca con Google

Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3):1215. Cerca con Google

Missiaen L, Robberecht W, van den Bosch L, et al. Abnormal intracellular Ca2+ homeostasis and disease. Cell Calcium. Review.2000; 28(1):1-21. Cerca con Google

Monserrat L, Ortiz-genga M, Lesende I, et al. Genetics of cardiomyopathies: novel perspectives with next generation sequencing. Curr Pharm Des. 2015; 21(4):418-30. Cerca con Google

Morton NE. Sequential tests for the detection of linkage. Am J Hum Genet. 1955; 7(3):277-318. Cerca con Google

Nasir K, Bomma C, Tandri H, et al. Electrocardiographic features of arrhythmogenic right ventricular dysplasia/cardiomyopathy according to disease severity: a need to broaden diagnostic criteria. Circulation. 2004; 110(12):1527-34. Cerca con Google

Nava A, Thiene G, Canciani B, et al. Familial occurrence of right ventricular dysplasia: a study involving nine families. J Am Coll Cardiol. 1988; 12(5): 1222-8. Cerca con Google

Norgett EE, Hatsell SJ, Carvajal-Huerta L, et al. Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet. 2000; 9(18):2761-6. Cerca con Google

Norton N, Robertson P, Rieder M, et al.; National Heart, Lung and Blood Institute GO Exome Sequencing Project. Evaluating pathogenicity of rare variants from dilated cardiomyopathy in the exome era. Circ Cardiovasc Genet. 2012; 5(2):167-74. Cerca con Google

Ott J, Wang J, Leal SM. Genetic linkage analysis in the age of whole-genome sequencing. Nat Rev Genet. 2015; 16(5):275-284. Cerca con Google

Otten E, Asimaki A, Maass A, et al. Desmin mutations as a cause of right ventricular heart failure affect the intercalated disks. Heart Rhythm. 2010; 7(8):1058-64. Cerca con Google

Ozaki C, Obata S, Yamanaka H, Tominaga S, Suzuki ST. The extracellular domains of E- and N-cadherin determine the scattered punctate localization in epithelial cells and the cytoplasmic domains modulate the localization. J Biochem. 2010; 147(3):415-25. Cerca con Google

Palatinus JA, O'Quinn MP, Barker RJ, Harris BS, Jourdan J, Gourdie RG. ZO-1 determines adherens and gap junction localization at intercalated disks. Am J Physiol Heart Circ Physiol. 2011; 300(2):H583-94. Cerca con Google

Palka H and Green K. Roles of plakoglobin end domains in desmosome assembly. J Cell Sci. 1997; 110(19):2359-71. Cerca con Google

Paris M, Rouleau M, Pucéat M, Aberdam D. Regulation of skin aging and heart development by TAp63. Cell Death Differ. 2012;19(2):186-93. Cerca con Google

Perazzolo Marra M, Rizzo S, Bauce B, De Lazzari M, et al. Arrhythmogenic right ventricular cardiomyopathy. Contribution of cardiac magnetic resonance imaging to the diagnosis. Herz. 2015; 40(4):600-6. Cerca con Google

Perrot A, Hussein S, Ruppert V, et al. Identification of mutational hot spots in LMNA encoding lamin A/C in patients with familial dilated cardiomyopathy. Basic Res Cardiol. 2009; 104(1):90-9. Cerca con Google

Pieperhoff S and Franke WW. The area composita of adhering junctions connecting heart muscle cells of vertebrates. VI. Different precursor structures in non-mammalian species. Eur J Cell Biol. 2008; 87(7):413-30. Cerca con Google

Pilichou K, Nava A, Basso C, et al. Mutations in Desmoglein-2 Gene Are Associated With Arrhythmogenic Right Ventricular Cardiomyopathy. Circulation. 2006; 113(9):1171-79. Cerca con Google

Pilichou K, Remme CA, Basso C, et al. Myocyte necrosis underlies progressive myocardial dystrophy in mouse DSG2-related arrhythmogenic right ventricular cardiomyopathy. J Exp Med. 2009; 206(8):1787-802. Cerca con Google

Pinamonti B, Di Lenarda A, Sinagra G, Silvestri F, Bussani R, Camerini F. Long-term evolution of right ventricular dysplasia-cardiomyopathy. The Heart Muscle Disease Study Group. Am Heart J. 1995; 129(2):412-5. Cerca con Google

Pinamonti B, Miani D, Sinagra G et al. Familial right ventricular dysplasia with biventricular involvment and inflammatory infiltration. Heart Muscle Disease Study Group. Heart. 1996; 76(1):66-9. Cerca con Google

Pinamonti B, Pagnan L, Bussani R et al. Right ventricular dysplasia with biventricular involvement. Circulation. 1998; 98(18):1943-5. Cerca con Google

Pollard KS, Hubisz MJ, Rosenbloom KR, Siepel A. Detection of nonneutral substitution rates on mammalian phylogenies. Genome Res. 2010; 20(1):110-21. Cerca con Google

Posch MG, Posch MJ, Geier C, et al. A missense variant in desmoglein-2 predisposes to dilated cardiomyopathy. Mol Genet Metab. 2008; 95(1-2):74-80. Cerca con Google

Priori SG, Napolitano C, Tiso N, et al. Mutations in the cardiac ryanodine receptor gene (hRYR2) underlie catecholaminergic polymorphic ventricular tachycardia. DNA Seq. 2001; 103(2):196-200. Cerca con Google

Purcell S, Neale B, Todd-Brown K, et al. PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet. 2007; 81(3):559-75. Cerca con Google

Quarta G, Syrris P, Ashworth M, et al. Mutations in the Lamin A/C gene mimic arrhythmogenic right ventricular cardiomyopathy. Eur Heart J. 2012; 33(9):1128-36. Cerca con Google

Rampazzo A, Nava A, Malacrida S, et al. Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet. 2002; 71(5):1200-06. Cerca con Google

Rampazzo a., Calore M, van Hengel J, van Roy F. Intercalated Discs and Arrhythmogenic Cardiomyopathy. Circ Cardiovasc Genet. 2014; 7(6):930-40. Cerca con Google

Rehm HL. Disease-targeted sequencing: a cornerstone in the clinic. Nat Rev Genet. 2013; 14(4):295-300. Cerca con Google

Robinson P, Griffiths PJ, Watkins H, Redwood CS. Dilated and hypertrophic cardiomyopathy mutations in troponin and alpha-tropomyosin have opposing effects on the calcium affinity of cardiac thin filaments. Circ Res. 2007; 101(12):1266-73. Cerca con Google

Romero J, Mejia-Lopez E, Manrique C, Lucariello R. Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC/D): A Systematic Literature Review. Clin Med Insights Cardiol. 2013; 7:97 114. Cerca con Google

Ross SE, Hemati N, Longo KA, et al. Inhibition of adipogenesis by Wnt signaling. Science. 2000; 289(5481):950-3. Cerca con Google

Ruiz P, Brinkmann V, Ledermann B, et al. Targeted mutation of plakoglobin in mice reveals essential functions of desmosomes in the embryonic heart. J Cell Biol. 1996; 135(1):215-25. Cerca con Google

Saffitz JE. Dependence of electrical coupling on mechanical coupling in cardiac myocytes. Insights gained from cardiomyopathies caused by defects in cell-cell communication. Ann NY Acad Sci. 2005; 1047:336-44. Cerca con Google

Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977; 74(12):5463-7. Cerca con Google

Sarparanta J, Blandin G, Charton K, et al. Interactions with M-band titin and calpain 3 link myospryn (CMYA5) to tibial and limb-girdle muscular dystrophies. J Biol Chem. 2010; 285(39):30304-315. Cerca con Google

Sato PY, Musa H, Coombs W, et al. Loss of plakophilin-2 expression leads to decreased sodium current and slower conduction velocity in cultured cardiac myocytes. Circ Res. 2009; 105(6):523-26. Cerca con Google

Sato PY, Coombs W, Lin X, et al. Interactions between ankyrin-G, plakophilin-2, and connexin43 at the cardiac intercalated disc. Circ Res. 2011; 109(2):193-201. Cerca con Google

Sen-Chowdhry S, Syrris P, Ward D, Asimaki A, Sevdalis E, McKenna WJ. Clinical and Genetic Characterization of Families With Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Provides Novel Insights Into Patterns of Disease Expression. Circulation. 2007; 115(13):1710-20. Cerca con Google

Shendure J and Ji H. Next-generation DNA sequencing. Nat Biotechnol. 2008; 26(10):1135-45. Cerca con Google

Sikkema-Raddatz B, Johansson LF, de Boer EN, et al. Targeted Next-Generation Sequencing can Replace Sanger Sequencing in Clinical Diagnostics. Hum Mutat. 2013; 34(7):1035-42. Cerca con Google

Simpson MA, Mansour S, Ahnood D, et al. Homozygous mutation of desmocollin-2 in arrhythmogenic right ventricular cardiomyopathy with mild palmoplantar keratoderma and woolly hair. Cardiology. 2009; 113(1):28-34. Cerca con Google

Spielmann M, Klopocki E. CNVs of noncoding cis-regulatory elements in human disease. Curr Opin Genet Dev. 2013; 23(3):249-56. Cerca con Google

Stokes DL and Wagenknecht T. Calcium transport across the sarcoplasmic reticulum: structure and function of Ca2+-ATPase and the ryanodine receptor. Eur J Biochem. Review. 2000; 267(17):5274-9. Cerca con Google

Swope D, Cheng L, Gao E, Li J, Radice GL. Loss of Cadherin-Binding Proteins β-Catenin and Plakoglobin in the Heart Leads to Gap Junction Remodeling and Arrhythmogenesis. Mol Cell Biol. 2012; 32(6):1056-67. Cerca con Google

Syrris P, Ward D, Evans A, et al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. Am J Hum Genet. 2006; 79(5): 978-84. Cerca con Google

Tandri H, Saranathan M, Rodriguez ER, et al. Noninvasive detection of myocardial fibrosis in arrhythmogenic right ventricular cardiomyopathy using delayed-enhancement magnetic resonance imaging. J Am Coll Cardiol. 2005; 45(1):98-103. Cerca con Google

Tandri H, Macedo R, Calkins H, et al. Role of magnetic resonance imaging in arrhythmogenic right ventricular dysplasia: insights from the North American arrhythmogenic right ventricular dysplasia (ARVD/C) study. Am Heart J. 2008; 155(1):147-53. Cerca con Google

Taylor M, Graw S, Sinagra G, et al. Genetic variation in titin in arrhythmogenic right ventricular cardiomyopathy-overlap syndromes. Circulation. 2011; 124(8):876-85. Cerca con Google

Thiele H and Nurnberg P. HaploPainter: a tool for drawing pedigrees with complex haplotypes. Bioinformatics. 2005; 21(8):1730-2. Cerca con Google

Thiene G, Nava A, Corrado D, et al. Right ventricular cardiomyopathy and sudden death in young people. N Engl J Med. 1988; 318:129-33. Cerca con Google

Thiene G, Nava A, Angelini A, Daliento L, Scognamiglio R, Corrado D. Anatomoclinical aspects of arrhythmogenic right ventricular cardiomyopathy. In Advances in cardiomyopathies. Edited by Baroldi G, Camerini F, Goodwin JF. Milano: Springer Verlag; 1990:397-408. Cerca con Google

Thiene G, Corrado D, Nava A, et al. Right ventricular cardiomyopathy: is there evidence of an inflammatory aetiology? Eur Heart J. 1991; 12 Suppl D: 22-5. Cerca con Google

Thiene G, Basso C, Danieli GA, Rampazzo A, Corrado D, Nava A. Arrhythmogenic right ventricular cardiomyopathy: a still underrecognised clinical entity. Trends Cardiovascular Med. 1997; 7(3):84-90. Cerca con Google

Thiene G, Corrado D, Basso C. Arrhythmogenic right ventricular cardiomyopathy/dysplasia. Orphanet J Rare Dis. 2007; 2(1):45. Cerca con Google

Thiene G, Nava A, Angelini A et al. Anatomo-clinical aspects of arrhythmogenic right ventricular cardiomyopathy. In: Baroldi G, Camerini F, Goodwin JF (eds) Advances in cardiomyopathies. Springer Verlag, pp 397-408. Cerca con Google

Thorvaldsdóttir H, Robinson JT, Mesirov JP. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform. 2013; 14(2):178-92. Cerca con Google

Tiso N, Stephan DA, Nava A, et al. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet. 2001; 10(3):189-94. Cerca con Google

Toyofuku T, Yabuki M, Otsu K, Kuzuya T, Hori M, Tada M. Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes. J Biol Chem. 1998; 273(21):12725-31. Cerca con Google

Turrini P, Corrado D, Basso C, Nava A, Bauce B, Thiene G. Dispersion of ventricular depolarization-repolarization: a non-invasive marker for risk stratification in arrhythmogenic right Cerca con Google

ventricular cardiomyopathy. Circulation. 2001; 103(25):3075-80. Cerca con Google

Uhl HS. A previously undescribed congenital malformation of the heart: almost total absence of the myocardium of the right ventricle. Bull John Hopkins Hosp. 1952; 91(3):197-209. Cerca con Google

van Tintelen JP, Entius MM, Bhuiyan ZA, et al. Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation. 2006; 113(13):1650-8. Cerca con Google

Valente M, Calabrese F, Thiene G, et al. In vivo evidence of apoptosis in arrhythmogenic right ventricular cardiomyopathy. Am J Pathol. 1998; 152(2):479-84. Cerca con Google

Valenzise M, Arrigo T, De Luca F, et al. R298Q mutation of p63 gene in autosomal dominant ectodermal dysplasia associated with arrhythmogenic right ventricular cardiomyopathy. Eur J Med Genet. 2008; 51(5):497-500. Cerca con Google

van Bokhoven H, McKeon F. Mutations in the p53 homolog p63: allele-specific developmental syndromes in humans. Trends Mol Med. 2002; 8(3):133-9. Cerca con Google

van der Zwaag PA, Jongbloed JD, van den Berg MP, et al. A genetic variants database for arrhythmogenic right ventricular dysplasia/cardiomyopathy. Hum Mutat. 2009; 30(9):1278-83. Cerca con Google

van der Zwaag PA, van Rijsingen IAW, Asimaki A, et al. Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy. Eur J Heart Fail. 2012; 14(11):1199-1207. Cerca con Google

van Hengel J, Calore M, Bauce B, et al. Mutations in the area composita protein alphat-catenin are associated with arrhythmogenic right ventricular cardiomyopathy. Eur Heart J. 2013; 34(3):201-10. Cerca con Google

van Spaendonck-Zwarts KY, van der Kooi AJ, van den Berg MP, et al. Recurrent and founder mutations in the Netherlands: the cardiac phenotype of DES founder mutations p.S13F and p.N342D. Neth Heart J. 2012; 20(5):219-28. Cerca con Google

van Tintelen JP, Entius MM, Bhuiyan ZA, et al. Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation. 2006; 113(13):1650-8. Cerca con Google

van Tintelen JP, Van Gelder IC, Asimaki A, et al. Severe cardiac phenotype with right ventricular predominance in a large cohort of patients with a single missense mutation in the DES gene. Heart Rhythm. 2009; 6(11):1574-83. Cerca con Google

Wang CK, Pan L, Chen J, Zhang M. Extensions of PDZ domains as important structural and functional elements. Protein Cell. 2010; 1(8):737-51. Cerca con Google

Wang H, Leinwand LA, Anseth KS. Roles of transforming growth factor-β1 and OB-cadherin in porcine cardiac valve myofibroblast differentiation. FASEB J. 2014; 28(10):4551-62. Cerca con Google

Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010; 38(16):e164. Cerca con Google

Whittock NV, Ashton GH, Dopping-Hepenstal PJ, et al. Striate palmoplantar keratoderma resulting from desmoplakin haploinsufficiency. J Invest Dermatol. 1999; 113(6):940-6. Cerca con Google

Wichter T, Paul M, Wollmann C, et al. Implantable cardioverter/defibrillator therapy in arrhythmogenic right ventricular cardiomyopathy. Single-center experience of long-term folow-up and complications in 60 patients. Circulation. 2004; 109(12):1503-8. Cerca con Google

Xu T, Yang Z, Vatta M, et al. Compound and digenic heterozygosity contributes to arrhythmogenic right ventricular cardiomyopathy. J Am Coll Cardiol. 2010; 55(6):587-97. Cerca con Google

Yang A, Kaghad M, Wang Y, et al. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell. 1998; 2(3):305-16. Cerca con Google

Yang Z, Bowles NE, Scherer SE, et al. Desmosomal dysfunction due to mutations in desmoplakin causes arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Res. 2006; 99(6):646-55. Cerca con Google

Yoerger DM, Marcus F, Sherrill D, et al. Echocardiographic findings in patients meeting task force criteria for arrhythmogenic right ventricular dysplasia: new insights from the multidisciplinary study of right ventricular dysplasia. Am Coll Cardiol. 2005; 15;45(6):860-5. Cerca con Google

Yoshida M, Romberger DJ, Illig MG, et al. Transforming growth factor-beta stimulates the expression of desmosomal proteins in bronchial epithelial cells. Am J Respir Cell Mol Biol. 1992; 6(4):439-45. Cerca con Google

Zhurinsky J, Shtutman M and Avri Ben-Ze’ev. Plakoglobin and β-catenin: protein interactions, regulation and biological roles. Journal of Cell Science. 2000; 113(18):3127-39. Cerca con Google

Zou J, Cao K, Yang B, et al. Dynamic substrate mapping and ablation of ventricular tachycardias in right ventricular dysplasia. J Interv Card Electrophysiol. 2004; 11(1):37-45. Cerca con Google

Cerca con Google

Solo per lo Staff dell Archivio: Modifica questo record