title: Mutation analysis of the G4.5 gene in patients with isolated left ventricular noncompaction.
abstract: Mutations in the gene G4.5, originally associated with Barth syndrome, have been reported to result in a wide spectrum of severe infantile X-linked cardiomyopathies. The purpose of this study was to investigate patients with isolated left ventricular noncompaction (LVNC) for disease-causing mutations in G4.5. In 27 patients including 10 families with isolated LVNC, mutation analysis of G4.5 was performed using single-strand DNA conformation polymorphism (SSCP) analysis and DNA sequencing. A novel splice acceptor site mutation of intron 8 of G4.5 was identified in a family with severe infantile X-linked LVNC without the usual findings of Barth syndrome. This mutation results in deletion of exon 9 from the mRNA, and is predicted to significantly disrupt the protein product. Genotype-phenotype correlation of G4.5 mutations in all 38 cases reported in the literature to date revealed that there was no correlation between location or type of mutation and either cardiac phenotype or disease severity. We suggest that males presenting with cardiomyopathy, particularly during infancy, even in the absence of the typical signs of Barth syndrome, should be evaluated for mutations in G4.5.
authors.affiliation: Department of Pediatrics, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Tohru
authors.initials: T
authors.lastname: Tsuji
authors.forename: Fukiko
authors.initials: F
authors.lastname: Ichida
authors.forename: Karla R
authors.initials: KR
authors.lastname: Bowles
authors.forename: Xianyi
authors.initials: X
authors.lastname: Yu
authors.forename: Sayaka
authors.initials: S
authors.lastname: Watanabe
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hirono
authors.forename: Shinichi
authors.initials: S
authors.lastname: Tsubata
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hamamichi
authors.forename: Jun
authors.initials: J
authors.lastname: Ohta
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Imai
authors.forename: Neil E
authors.initials: NE
authors.lastname: Bowles
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
mesh_terms: D000217:Acyltransferases; D009202:Cardiomyopathies / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D040181:Genetic Diseases, X-Linked; D005838:Genotype; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D014157:Transcription Factors
chemical_list: D011506:Proteins; D014157:Transcription Factors; D000217:Acyltransferases; C108675:TAFAZZIN protein, human