TBX5基因在中国人心手综合征患者中的突变分析

TBX5 mutation in Chinese patients with Holt-Oram syndrome

目的 检测中国心手综合征患者 TBX5基因突变。方法 利用单链构象多态性分析和测序方法 ,对 7个心手综合征患者家系进行 TBX5基因突变检测。结果 发现 3个家系患者有单链构象多态性改变 ,经测序证实为 3个新位点基因突变 :1个心手综合征家系患者为 TBX5基因单个碱基缺失引起移码突变 ,2个心手综合征家系为 TBX5基因碱基替换引起错义突变。结论 中国人 TBX5基因突变可引起心手综合征。

Objective To analyse TBX5 mutation in Chinese patients with Holt Oram syndrome(HOS). Methods Seven HOS families were analysed with single strand conformation polymorphism(SSCP) and sequencing. Results Three SSCP changes were detected and identified as the TBX5 gene mutation at three new sites. One of the changes is a frameshift mutation caused by a base cytidine deletion at the cDNA sequence of 416, which altered all the codons after the point, thus it can not encode the protein of normal amino acid sequence; another is a missense mutation induced by a base substitution(C→A) at the cDNA sequence of 145, which made the codon of that point change from CAG→AAG, and encoded amino acid changed from glutamine(Gln) to lysine(Lys), consequently the change weakened the function of TBX5 protein; the third is also a missense mutation which resulted from a base substitution (T→C) at the cDNA sequence of 161, this change made the codon of that point change from ATC→ACC, it changed the encoded amino acid from isoleucine(Ile) to threonine(Thr), which reduced the function of TBX5 protein. Conclusion HOS in Chinese is caused by mutation in TBX5.