Structural analysis of the titin gene in hypertrophic cardiomyopathy: Identification of a novel disease gene
Structural analysis of the titin gene in hypertrophic cardiomyopathy: Identification of a novel disease gene
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DOI：
10.1006/bbrc.1999.1221
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发表时间：
1999-08-27
影响因子：
3.1
通讯作者：
Kimura, A
中科院分区：
文献类型：
--
作者：
Satoh, M;Takahashi, M;Kimura, A
肥厚型心肌病(HCM)以心肌肥厚伴肌原纤维紊乱为特征。分子遗传学分析表明肥厚型心肌病由8个不同的基因突变引起，然而这些疾病基因的突变可在约一半的肥厚型心肌病患者中发现，提示存在其他未知的疾病基因(S)，由于已知的疾病基因编码在心肌中表达的肌节蛋白，我们在82例已知疾病基因未突变的肥厚型心肌病患者中寻找与疾病相关的Titin基因突变。1例患者740位密码子A G：T由CGC变为CTC，用亮氨酸代替精氨酸。在500多条正常染色体中未发现该突变，在酵母双杂交实验中增加了肌动蛋白与α-肌动蛋白的结合亲和力。这些观察表明，肌动蛋白突变可能通过改变对α-肌动蛋白的亲和力而导致该患者的肥厚型心肌梗死。(C)1999年学术出版社。
Hypertrophic cardiomyopathy (HCM) is characterized by ventricular hypertrophy accompanied by myofibrillar disarrays. Molecular genetic analyses have revealed that mutations in 8 different genes cause HCM, Mutations in these disease genes, however, could be found in about half of HCM patients, suggesting that there are other unknown disease gene(s), Because the known disease genes encode sarcomeric proteins expressed in the cardiac muscle, we searched for a disease-associated mutation in the titin gene in 82 HCM patients who had no mutation in the known disease genes. A G: to T transversion in codon 740, from CGC to CTC, replacing Arginine with Leucine was found in a patient. This mutation was not found in more than 500 normal chromosomes and increased the binding affinity of titin to alpha-actitin in the yeast two-hybrid assay. These observations suggest that the titin mutation may cause HCM in this patient via altered affinity to alpha-actinin. (C) 1999 Academic Press.