Genetic analysis of sarcmere in left ventricular noncompaction

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591571
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: University of Toyama
• Principal Investigator: ICHIDA Fukiko 富山大学, 大学院医学薬学研究部(医学), 准教授 (30223100)
• Co-Investigator(Kenkyū-buntansha): OZAWA Sayaka 富山大学, 大学病院, 診療助手 (40596540) ; SAITO Kazuyoshi 富山大学, 大学病院, 助教 (30566097) ; HATA Yukiko 富山大学, 大学院医学薬学研究部(医学), 助教 (30311674) ; NISHIDA Nnaoki 富山大学, 大学院医学薬学研究部(医学), 教授 (10315088)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 心筋症 / 遺伝子異常 / サルコメア遺伝子 / 心筋発達 / 心筋緻密化障害

Outline of Final Research Achievements

We investigated 80 Japanese patients with a clinical diagnosis of LVNC, and identified 27 sarcomeric gene mutations in 25 patients (28%). MYH7 and MYBPC3 were the most prevalent disease genes and accounts for 75% of cases with mutation. Of note, 3 infantile cases and 2 juvenile cases were compound or double heterozygotes for 2 different mutations, and showed the most severe phenotypes including heart transplantation, death or cardiopulmonary arrest. Patients with single mutations in TPM1 and ACTC1 showed similar poor prognosis. Comparing sarcomere mutation-positive and mutation-negative LVNC probands showed no significant differences with respect to clinical characteristics at baseline and mortality during follow up. Mutations in sarcomere genes account for a significant proportion of cases of LVNC in this cohort. The presence of a mutation in TPM1 or ACTC1, or compound heterozygosity for mutations in other sarcomere genes in LVNC are associated with the most severe clinical phenotype.

Free Research Field

小児循環器学