腓骨肌萎缩症SIMPLE基因突变分析

MUTATION ANALYSIS OF SIMPLE GENE WITH CHARCOT -MARIE -TOOTH DISEASE

目的探讨脂多糖诱导的肿瘤坏死因子α(lipolysaccharide-induced tumor necrosis factor-alphafactor,LITAF/SIMPLE)基因在中国人腓骨肌萎缩症的突变特点。方法应用聚合酶链反应(polymerase chainreaction,PCR)、DNA直接测序和限制性内切酶酶切技术,对已经排除PMP22的大片段重复突变和PMP22、MPZ、Cx32、NEFL、GDAP1、Hsp22、Hsp27点突变的6个常染色体显性遗传的腓骨肌萎缩症家系先证者和27个散发病例共33例患者进行SIMPLE基因突变分析,对100例健康对照者进行PCR、限制性内切酶酶切。结果 1例散发患者检测出一个新的SIMPLE基因单核苷酸改变(G269A),位于3号外显子的G→A,导致所编码的氨基酸由精氨酸变为组氨酸(A90H),7例健康对照者等位基因同样具有此改变,说明为一种多态;另1例患者发现A274G,国外学者已证实为人群中常见的多态。结论 SIMPLE基因突变可能在我国腓骨肌萎缩症患者中少见;SIMPLE基因G269A为新发现的多态。

Objective To detect mutations of SIMPLE gene in Chinese patients with Charcot - Marie- Tooth disease （CMT）. Methods Thirty -there patients with CMT were examined, each of whom tested negative for other known gene mutations, including the duplication of PMP22 and point mutations of PMP22 、MPZ 、Cx32、NEFL、GDAP1 、Hsp22 and Hsp27. The mutations in SIMPLE gene from 33 CMT patients and 100 healthy controls were detected using polymerase chain reaction（PCR）, DNA sequence analysis, and restriction enzyme digestion analysis. Results A new nucleotide variation G269A in exon 3 was found in a sporadic patient and it leads to substitution of arginine for histidine at amino acid 90（A90H）. This nucleotide variation was also found in 7 healthy controls,which was proved a new polymorphism. Another nucleotide variation A274G was found in another sporadic patient, which had been identified as a polymorphism by researcher. Conclusion The mutation in SIMPLE gene is not common in Chinese patients with CMT. G269A a new found polymorphism in SIMPLE.