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Two Novel Homozygous Desmoplakin Mutations in Carvajal Syndrome
Author(s) -
MolhoPessach Vered,
Sheffer Sivan,
Siam Rula,
Tams Spiro,
Siam Ihab,
Awwad Rula,
Babay Sofia,
Golender Julius,
Simanovsky Natalia,
Ramot Yuval,
Zlotogorski Abraham
Publication year - 2015
Publication title -
pediatric dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.542
H-Index - 73
eISSN - 1525-1470
pISSN - 0736-8046
DOI - 10.1111/pde.12541
Subject(s) - desmoplakin , palmoplantar keratoderma , plakoglobin , exome sequencing , medicine , genetics , arrhythmogenic right ventricular dysplasia , mutation , exome , omim : online mendelian inheritance in man , cardiomyopathy , phenotype , pathology , gene , biology , hyperkeratosis , heart failure , wnt signaling pathway , catenin
Background Mutations in various desmosomal proteins were shown to cause inherited forms of cardiomyopathy. Carvajal syndrome (Online Mendelian Inheritance in Man [ OMIM ] 605676) is characterized by the association of dilated cardiomyopathy, striate palmoplantar keratoderma, and woolly hair. It is caused by homozygous as well as heterozygous mutations in DSP , which encodes the desmosomal plaque protein desmoplakin. An overlapping cardiocutaneous phenotype was also described with homozygous mutations in genes encoding two other desmosomal proteins; plakoglobin (Naxos disease; OMIM 601214) and desmocollin‐2 ( OMIM 610476). Methods We performed clinical and molecular workups in two consanguineous Arab Palestinian families manifesting an autosomal recessive pattern of inheritance of the above mentioned clinical findings. Whole exome sequencing was employed in the search for the causing mutation. Results Affected family members suffered from biventricular involvement and arrhythmogenic right ventricular dysplasia based on echocardiography and magnetic resonance imaging. One patient who underwent implantation of an implantable cardioverter‐defibrillator ( ICD ) is still alive at the age of 59 years. Whole exome sequencing revealed two novel homozygous mutations in DSP , each affecting one family. Conclusions The association of woolly hair with palmoplantar keratoderma in a child should lead to a cardiac workup in the search for those at increased risk for sudden cardiac death. Early diagnosis and ICD implantation may be lifesaving. Whole exome sequencing should be utilized for rapid genetic analysis since the cardiocutaneous phenotype may result from mutations in one of several genes.