Dermatology Commons^™

Arrhythmogenic Right Ventricular Cardiomyopathy In Patients With Biallelic Jup-Associated Skin Fragility., Hassan Vahidnezhad, Leila Youssefian, Masoomeh Faghankhani, Nikoo Mozafari, Amir Hossein Saeidian, Fatemeh Niaziorimi, Fahimeh Abdollahimajd, Soheila Sotoudeh, Fateme Rajabi, Liaosadat Mirsafaei, Zahra Alizadeh Sani, Lu Liu, Alyson Guy, Sirous Zeinali, Ariana Kariminejad, Reginald T. Ho, John A Mcgrath, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

Arrhythmogenic right ventricular cardiomyopathy (ARVC), with skin manifestations, has been associated with mutations in JUP encoding plakoglobin. Genotype-phenotype correlations regarding the penetrance of cardiac involvement, and age of onset have not been well established. We examined a cohort of 362 families with skin fragility to screen for genetic mutations with next-generation sequencing-based methods. In two unrelated families, a previously unreported biallelic mutation, JUP: c.201delC; p.Ser68Alafs*92, was disclosed. The consequences of this mutation were determined by expression profiling both at tissue and ultrastructural levels, and the patients were evaluated by cardiac and cutaneous work-up. Whole-transcriptome sequencing by RNA-Seq revealed JUP as …