| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Research Abstract |
Isolated left ventricular noncompaction (LVNC) is rare, and usually presents in infancy with a hypertrophic and dilated left ventricle with deep trabeculations and, commonly, with reduced systolic function. In isolated LVNC, familial recurrence is high and found in approximately 40% of the patients (Ichida et al. Am J Coll Cardiol 1999). Genetic linkage and mutation analysis have revealed that mutations in the gene G4.5, originally associated with Barth syndrome, are responsible for LVNC (Ichida et al. Circulation 2001). However, mutations in G4.5 may result in a wide phenatypic spectrum of severe X-linked infantile cardiomyopathies. The incidence of G4.5 mutations associated with each cardiac phenotype is unknown, and genotype and phenotype correlations have not been fully evaluated (Chen et al., Molecular Genetics and Metabolism, 2002). The purpose of this study was to investigate patients with severe X-linked infantile cardiomyopathies and isolated 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.
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