常染色体隐性遗传性羊毛状发一家系基因突变检测

Gene mutation analysis in a Chinese pedigree with autosomal recessive woolly hair

目的检测1个常染色体隐性遗传性羊毛状发家系的致病基因。方法收集1个中国汉族常染色体隐性遗传性羊毛状发家系2例患者及其他家族成员的临床资料,采集他们的外周血和100例健康人外周血,提取DNA。应用二代皮肤靶向测序包检测患者的基因突变,然后采用Sanger测序验证,对突变基因编码蛋白质进行功能预测。结果2例患者均在LIPH基因存在错义突变c.530T>G(p.Leu177Arg)和c.736T>A(p.Cys246Ser),这2个突变分别来自患者父母,而100例健康对照中均未发现此2种突变。物种间序列比对分析发现,LIPH基因所编码蛋白质第177位亮氨酸和第246位半胱氨酸均属于高度保守的序列,SIFT和Polyphen-2软件预测c.530T>G(p.Leu177Arg)和c.736T>A(p.Cys246Ser)突变均为有害变异位点。结论LIPH基因的错义突变c.530T>G(p.Leu177Arg)和c.736T>A(p.Cys246Ser)可能为引起该家系羊毛状发患者临床表型的致病基因。

Objective To identify causative genes for autosomal recessive woolly hair(ARWH)in a family.Methods Clinical data were collected from two patients and other family members in a Chinese pedigree of Han nationality with ARWH.Peripheral blood samples were obtained from the two patients,their unaffected parents and 100 unrelated healthy individuals,and DNA was extracted from the blood samples.A next-generation skin-targeted sequencing panel was used to detect gene mutations in the patients,and Sanger sequencing was performed to verify the sequencing results.The function of protein encoded by the mutant gene was predicted.Results Two missense mutations c.530T>G(p.Leu177Arg)and c.736T>A(p.Cys246Ser)were both identified in the LIPH gene of the two patients,which were inherited from their father and mother respectively.Neither of the two mutations was identified in the 100 unrelated healthy controls.Interspecies sequence alignment showed that leucine at amino acid position 177 and cysteine at amino acid position 246 of the protein encoded by the LIPH gene were highly evolutionarily conserved.As SIFT and Polyphen-2 softwares showed,the mutations c.530T>G(p.Leu177Arg)and c.736T>A(p.Cys246Ser)were both predicted to be detrimental variations.Conclusion Two missense mutations c.530T>G(p.Leu177Arg)and c.736T>A(p.Cys246Ser)in the LIPH gene may contribute to the clinical phenotype of the two patients with ARWH in this family.