title: Identification of a novel mutation V2321M of the cardiac ryanodine receptor gene of sudden unexplained death and a phenotypic study of the gene mutations.
abstract: Mutations of the cardiac ryanodine receptor (RyR2) gene cause catecholaminergic polymorphic ventricular tachycardia, which sometimes results in a finding of sudden unexplained death (SUD) at autopsy. We found a novel mutation (V2321M) in exon 46 of the RyR2 gene in a SUD case. V2321M was localized in a highly conservative site of the RyR2 gene, but was not found in 400 reference alleles. We previously reported two SUD cases with R420W mutations in exon 14 of the RyR2 gene. We examined possible phenotypic characteristics of all three of these cases of SUD with the RyR2 gene mutations. All cases displayed mesenteric lymph node hypertrophy as well as tendencies for aortic narrowing. By contrast, only one of the 14 SUD cases without RyR2 mutations displayed these phenotypes. This study supports the concept that postmortem genetic testing of RyR2 mutations should be considered in autopsy examinations of SUD cases. It also raises the possibility that some cases with RyR2 mutations may display phenotypic changes in lymphoid and cardiovascular organs.
authors.affiliation: Department of Legal Medicine, Osaka Medical College, Takatsuki 569-8686, Japan. leg010@art.osaka-med.ac.jp
authors.forename: Hajime
authors.initials: H
authors.lastname: Nishio
authors.forename: Misa
authors.initials: M
authors.lastname: Iwata
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Tamura
authors.forename: Tokiko
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Kento
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000293:Adolescent; D000311:Adrenal Glands / Q000473:pathology; D000328:Adult; D001011:Aorta / Q000473:pathology; D002648:Child; D003251:Constriction, Pathologic / Q000473:pathology; D004252:DNA Mutational Analysis; D003645:Death, Sudden / Q000209:etiology*; D005091:Exons; D005260:Female; D053803:Forensic Genetics; D049429:Forensic Pathology; D005820:Genetic Testing; D006801:Humans; D006984:Hypertrophy; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D020125:Mutation, Missense; D009929:Organ Size; D010641:Phenotype; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013154:Spleen / Q000473:pathology; D055815:Young Adult
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel