常染色体隐性遗传性少毛症7型1例并文献复习

A case of autosomal recessive hypotrichosis type 7 and literature review

目的 报告常染色体隐性遗传性少毛症7型1例,探讨该家系LIPH基因突变情况。方法 收集患者临床资料,采集患者及其父母外周血,提取基因组DNA,采用高通量测序法检测全部基因编码区域的各外显子序列突变情况,确定基因突变位点,对突变基因进行PCR-Sanger测序验证和生物信息学分析。结果 患者存在LIPH基因2号外显子c.409C>T(p.Gln137^(*))和6号外显子c.742C>A(p.His248Asn)复合杂合突变,2个突变分别来自患者父母,其中c.409C>T(p.Gln137^(*))既往未见报道。生物信息学分析示:对比多物种LIPH基因编码的第137位谷氨酰胺和第248位组氨酸均属于高度保守的序列,2个位点突变后的蛋白结构与野生型蛋白存在差异,ACMG指南评级2个突变为疑似致病变异。结论 LIPH基因2号外显子c.409C>T(p.Gln137^(*))和6号外显子c.742C>A(p.His248Asn)复合杂合突变是本例常染色体隐性遗传性少毛症7型的致病原因。

Objective To report a case of autosomal recessive hypotrichosis type 7,and to discuss the mutations of LIPH gene in this family.Methods The clinical data of the case were collected.The genomic DNA was extracted from the peripheral blood of the patient and her parents.The high-throughput sequencing method was used to detect the sequence mutations of each exon in the coding region of all genes,and the gene mutation sites were determined.The mutant genes were verified by PCR-Sanger sequencing and bioinformatics analysis.Results The patient had a compound heterozygous mutations of LIPH gene c.409C>T(p.Gln137^(*))in exon 2 and c.742C>A(p.His248Asn)in exon 6,which were from the patient′s father and mother,respectively.c.409C>T(p.Gln137^(*))had not been reported before.The results of bioinformatics analysis showed that the 137th Gln sequence and 248th His sequence of LIPH protein were highly conserved in multiple species.The structures of the corresponding proteins were altered after the mutation of the two sites compared to wild-type proteins,and the two mutations were suspected to be pathogenic mutations according to ACMG guidelines.Conclusion The compound heterozygous mutations of LIPH gene c.409C>T(p.Gln137^(*))in exon 2 and c.742C>A(p.His248Asn)in exon 6 are the cause of autosomal recessive hypotrichosis type 7 in this case.