2001 Fiscal Year Final Research Report Summary
Genetic analysis of left ventricular noncompaction
| Project/Area Number |
12670734
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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 | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
ICHIDA Fukiko Toyama Medical & Pharmaceutical University, Faculty of Medicine, Associate professor, 医学部, 助教授 (30223100)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Cardiomyopathy / Left ventricular noncompaction / Fatal myocardium / α -Dystrobrevin / G4.5 / Autosomal dominant transmission |
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| Research Abstract |
Left ventricular noncompaction (LVNC) is a new clinical entity of cardiomyopathy, thought to be due to an arrest of myocardial morphogenesis in the early period of embryogenesis. The long-term prognosis, hemodynamic properties and genetic nature of LVNC remain largely unknown. Recent studies on genetic linkage analysis has revealed that mutations in the gene G4.5 on the Xq28 chromosomal region are responsible for LVNC and that this disorder is allelic with Earth syndrome. We identified and analyzed a large series of LVNC patients via a nationwide survey including the familial clusters in 40 % of the patients. Importantly, female cases of LVNC were observed in our series, suggesting the possible non-X-linked inheritance in some instances. We performed candidate gene screening in FKBP and G4.5, as well as cytoskeletal protein-encoding gene α -dystrobrevin, using SSCP (single strand conformation polymorphism) and DNA sequencing in 27 patients with LVNC. A C>T mutation was identified at nucleotide 362 of α -dystrobrevin, resulting in a change from proline to leucine (P121L) in all six affected individual from one family with LVNC, including five with non-isolated LVNC and one with isolated LVNC. The pattern of transmission is most consistent with an autosomal dominant trait over four generations. No mutations were identified in FKBP12 and G4.5 in these patients. These data suggest that there is genetic heterogeneity in LVNC, like dilated cardiomyopathy, is a diseasre of the cytoskeleton. This mutation in the α - dystrobrevin represents the first mutation identified in patients with LVNC.
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Research Products
(10 results)
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[Publications] Ichida F, Tsubata S, Bowles KR, Haneda N, Uese K, Miyawaki T, W Jeffrey Dreyer, John Messina, Dianc L Broom, Li H, Bowles NE, Towbin JA.: "Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome"Circulation. 103. 1256-1263 (2001)
Description
「研究成果報告書概要(欧文)」より
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