LIU Xing, RAO Li, ZHOU Bin, ZHANG Bei-lei, WANG Yan-yun, CHEN Bin, WU Yang, HUANG Ping
Department of Cardiology, West China Hospital of Sichuan University, Chengdu 610041, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2008 Dec;36(12):1066-9.
Titin is recently known as the largest protein which exists in the striated muscle sarcomere and is dynamic both in biomechanics properties and biochemical functions. Four possible disease-associated mutations located in three exons (3, 14, 49) of titin gene (TTN) have been identified in Japanese DCM patients in 2002. We observed the possible association of TTN mutation in Chinese patients with DCM.
Three exons of TTN (3, 14, 49) were screened in 117 DCM patients and 120 controls by polymerase chain reaction-single strand conformation polymorphisms (PCR-SSCP) and DNA sequence. SSCP was carried out following a protocol optimized for each PCR fragment after amplification. Abnormal SSCP results were subsequently confirmed by DNA sequencing.
The mutations reported in Japanese DCM patients were not identified in this patient cohort. A novel mutation [the G13053A (TTN cDNA sequence, X90568) change resulted in amino acid change at position 4351 (Gly4351Asp)] was found in two young DCM patients from a DCM family (1.7%). There was no similar mutation in controls.
This novel Gly4351Asp mutation in TTN might be associated with DCM.
肌联蛋白是目前已知存在于横纹肌肌节中的最大蛋白质，在生物力学特性和生化功能方面均具有动态性。2002年，在日本扩张型心肌病（DCM）患者中已鉴定出位于肌联蛋白基因（TTN）三个外显子（3、14、49）中的四种可能与疾病相关的突变。我们观察了中国DCM患者中TTN突变的可能关联。
通过聚合酶链反应-单链构象多态性（PCR-SSCP）和DNA测序，对117例DCM患者和120例对照者的TTN三个外显子（3、14、49）进行筛查。扩增后，按照针对每个PCR片段优化的方案进行SSCP。随后通过DNA测序确认异常的SSCP结果。
在该患者队列中未鉴定出日本DCM患者中报道的突变。在一个DCM家族的两名年轻DCM患者中发现了一种新的突变[G13053A（TTN cDNA序列，X90568）改变导致第4351位氨基酸改变（Gly4351Asp）]（1.7%）。对照组中没有类似突变。
TTN中这种新的Gly4351Asp突变可能与DCM有关。
