title: DSG2 mutations contribute to arrhythmogenic right ventricular dysplasia/cardiomyopathy.
abstract: 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.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Awad
authors.forename: Darshan
authors.initials: D
authors.lastname: Dalal
authors.forename: Eunpi
authors.initials: E
authors.lastname: Cho
authors.forename: Nuria
authors.initials: N
authors.lastname: Amat-Alarcon
authors.forename: Cynthia
authors.initials: C
authors.lastname: James
authors.forename: Crystal
authors.initials: C
authors.lastname: Tichnell
authors.forename: April
authors.initials: A
authors.lastname: Tucker
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Russell
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
authors.forename: Harry C
authors.initials: HC
authors.lastname: Dietz
authors.forename: Hugh
authors.initials: H
authors.lastname: Calkins
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
mesh_terms: 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
chemical_list: D017931:DNA Primers; C495314:DSG2 protein, human; D051301:Desmoglein 2