title: Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2).
abstract: Arrhythmogenic right ventricular dysplasia type 2 (ARVD2, OMIM 600996) is an autosomal dominant cardiomyopathy, characterized by partial degeneration of the myocardium of the right ventricle, electrical instability and sudden death. The disease locus was mapped to chromosome 1q42--q43. We report here on the physical mapping of the critical ARVD2 region, exclusion of two candidate genes (actinin 2 and nidogen), elucidation of the genomic structure of the cardiac ryanodine receptor gene (RYR2) and identification of RYR2 mutations in four independent families. In myocardial cells, the RyR2 protein, activated by Ca(2+), induces the release of calcium from the sarcoplasmic reticulum into the cytosol. RyR2 is the cardiac counterpart of RyR1, the skeletal muscle ryanodine receptor, involved in malignant hyperthermia (MH) susceptibility and in central core disease (CCD). The RyR2 mutations detected in the present study occurred in two highly conserved regions, strictly corresponding to those where mutations causing MH or CCD are clustered in the RYR1 gene. The detection of RyR2 mutations causing ARVD2, reported in this paper, opens the way to pre-symptomatic detection of carriers of the disease in childhood, thus enabling early monitoring and treatment.
authors.affiliation: Department of Biology, University of Padova, 35121 Padova, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Tiso
authors.forename: D A
authors.initials: DA
authors.lastname: Stephan
authors.forename: A
authors.initials: A
authors.lastname: Nava
authors.forename: A
authors.initials: A
authors.lastname: Bagattin
authors.forename: J M
authors.initials: JM
authors.lastname: Devaney
authors.forename: F
authors.initials: F
authors.lastname: Stanchi
authors.forename: G
authors.initials: G
authors.lastname: Larderet
authors.forename: B
authors.initials: B
authors.lastname: Brahmbhatt
authors.forename: K
authors.initials: K
authors.lastname: Brown
authors.forename: B
authors.initials: B
authors.lastname: Bauce
authors.forename: M
authors.initials: M
authors.lastname: Muriago
authors.forename: C
authors.initials: C
authors.lastname: Basso
authors.forename: G
authors.initials: G
authors.lastname: Thiene
authors.forename: G A
authors.initials: GA
authors.lastname: Danieli
authors.forename: A
authors.initials: A
authors.lastname: Rampazzo
mesh_terms: D000595:Amino Acid Sequence; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D009206:Myocardium / Q000378:metabolism*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D004247:DNA