2006 Fiscal Year Final Research Report Summary
Genetic analysis in infantile dilated cardiomyopathy and ventricular noncompaction 〜analysis of cytoskeletal protein genes〜
| Project/Area Number |
17591072
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | University of Toyama |
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Principal Investigator |
ICHIDA Fukiko University of Toyama, Faculty of Medicine, Associate Professor, 大学院医学薬学研究部, 准教授 (30223100)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUOKA Rumiko Tokyo Women's Medical College, Assistant Professor, 医学部, 講師 (50120051)
NISHIKAWA Toshiro Tokyo Women's Medical College, Associate Professor, 医学部, 准教授 (50120019)
JEFFREY A Towbin Baylor College of Medicine, Professor
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| Project Period (FY) |
2005 – 2006
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| Keywords | dilated cardiomyopathy / ventricular noncompaction / X-linked / autosomal dominant / cytoskeletal protein gene / LDB3 / G4.5 / DTNA |
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| Research Abstract |
Left ventricular noncompaction (LVNC) is a cardiomyopathy which represents the persistence of numerous excessively prominent ventricular trabeculations and deep intertrabecular recesses. To date, the etiology of this disorder is postulated to be caused by an arrest of the normal process of intrauterine endomyocardial morphogenesis. Although LVNC has only been recognized as a unclassified cardiomyopathy, two forms of this anomaly have been described, isolated LVNC which occurs in the absence of other cardiac anomalies and nonisolated LVNC in which similar myocardial anomaly is frequently reported in association with congenital heart diseases. Clinical manifestations in LVNC are highly variable, ranging from no symptoms to arrhythmias, heart failure, cardiac transplantation and dead. This study was performed to investigate Japanese LVNC patients for disease-causing mutations in a series of selected candidate genes. DNA was isolated from the peripheral 103 patients including 44 cases from
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20 families and 59 sporadic cases. DNA samples were screened for mutations in the genes encoding G4.5 (TAZ), α-dystrobrevin (D7NA), α1-syntrophin (STNA1), FK506 Binding Protein 1A (FKBP1A or FKPB12:FKBP 1A), and LIM Domain Binding protein 3 (Cypher/ZASP:LDB3), using single-strand conformational polymorphism analysis (SSCP) and DNA sequencing. DNA variants were identified in 17 of the 103 patients, including 15 cases from 4 families and 2 sporadic cases. A splice acceptor mutation of intron 8 in TAZ (IVS8-1G>C) was identified in one family with isolated LVNC, resulting in deletion of exon 9 from mRNA. In a sporadic case of isolated LVNC and Barth syndrome (BTHS), a 158insC in exon 2 of TAZ resulting in a frame-shift mutation was identified. A 1876G>A substitution changing an aspartic acid to asparagine (D626N) was identified in LDB3 in four members of two families with LVNC. A 163G>A polymorphism was identified in LDB3, which changed a valine to isoleucine (V551) in one patient with isolated LVNC. In addition, in a family with nonisolated LVNC, a 362C>T mutation was identified in DEM. LVNC, like other forms of inherited cardiomyopathy, is a genetically heterogeneous disease, associated with variable clinical symptoms and can be inherited as an autosomal or X-linked recessive disorder. Less
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