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A family with a complex clinical presentation characterized by arrhythmogenic right ventricular dysplasia/cardiomyopathy and features of branchio‐oculo‐facial syndrome
Author(s) -
Murray Brittney,
Wagle Rohan,
AmatAlarcon Nuria,
Wilkens Alisha,
Stephens Paul,
Zackai Elaine H.,
Goldmuntz Elizabeth,
Calkins Hugh,
Deardorff Matthew A.,
Judge Daniel P.
Publication year - 2013
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35733
Subject(s) - desmoplakin , arrhythmogenic right ventricular dysplasia , plakoglobin , cardiomyopathy , haploinsufficiency , desmosome , genetics , medicine , cardiology , biology , gene , heart failure , phenotype , wnt signaling pathway , cell , catenin
Abstract Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a familial form of cardiomyopathy typically caused by mutations in genes that encode an element of the cardiac desmosome. Branchio‐oculo‐facial syndrome (BOFS) is a craniofacial disorder caused by TFAP2A mutations. In a family segregating ARVD/C, some members also had features of BOFS. Genetic testing for ARVD/C identified a mutation in PKP2 , encoding plakophilin‐2, a component of the cardiac desmosome. Evaluation of dysmorphology by chromosome microarray (CMA) identified a 4.4 Mb deletion at chromosome 6p24 that included both TFAP2A and DSP , encoding desmoplakin, an additional component of the cardiac desmosome implicated in ARVD/C. A family member with both the 6p24 deletion and PKP2 mutation had more severe cardiac dysfunction. These findings suggest that this contiguous gene deletion contributes to both ARVD/C and BOFS, and that DSP haploinsufficiency may contribute to cardiomyopathy. This family provides a clinical example that underscores the need for careful evaluation in clinical scenarios where genetic heterogeneity is known to exist. Finally, it suggests that individuals with unexplained cardiomyopathy and dysmorphic facial features may benefit from CMA analysis. © 2013 Wiley Periodicals, Inc.