DSG2 mutations contribute to arrhythmogenic right ventricular dysplasia/cardiomyopathy.
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a disorder characterized by fibrofatty replacement of cardiac myocytes that typically manifests in the right ventricle. It is inherited as an autosomal dominant disease with reduced penetrance, although autosomal recessive forms of the disease also occur. We identified four probands with ARVD/C caused by mutations in DSG2, which encodes desmoglein-2, a component of the cardiac desmosome. No association between mutations in this gene and human disease has been reported elsewhere. One of these probands has compound-heterozygous mutations in DSG2, and the remaining three have isolated heterozygous missense mutations, each disrupting known functional components of desmoglein-2. We report that mutations in DSG2 contribute to the development of ARVD/C.
Awad
Mark M
MM
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Dalal
Darshan
D
Cho
Eunpi
E
Amat-Alarcon
Nuria
N
James
Cynthia
C
Tichnell
Crystal
C
Tucker
April
A
Russell
Stuart D
SD
Bluemke
David A
DA
Dietz
Harry C
HC
Calkins
Hugh
H
Judge
Daniel P
DP
D000595:Amino Acid Sequence; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics*; D001483:Base Sequence; D006332:Cardiomegaly / Q000235:genetics*; D017931:DNA Primers; D051301:Desmoglein 2 / Q000737:chemistry / Q000235:genetics*; D006352:Heart Ventricles / Q000473:pathology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; C495314:DSG2 protein, human; D051301:Desmoglein 2