眼皮肤白化病一家系基因突变分析

Mutation analysis in a pedigree with oculocutaneous albinism

目的 利用靶向二代测序技术对1个眼皮肤白化病家系进行基因突变分析。方法 收集1个眼皮肤白化病家系的临床资料，提取先证者及其父母外周血DNA。通过高通量测序技术，对先证者TYR、OCA2、TYRP1、SLC45A2等29个基因的外显子编码区进行直接测序，寻找可能存在的基因突变。以Sanger测序技术检测先证者父母的相应基因位点。结果 先证者TYR基因检测到2个杂合突变，分别是c.534G 〉 C（p.Trp178Cys）和c.1147G 〉 A（p.Asp383Asn）。其中c.534G 〉 C突变为新发突变，c.1147G 〉 A突变为已知致病突变。先证者父母TYR基因突变检测结果证实，先证者的c.534G 〉 C突变来自父亲，c.1147G 〉 A突变来自母亲。结论 应用靶向二代测序技术为一个眼皮肤白化病家系确定了TYR基因致病性新突变c.534G 〉 C。

Objective To investigate gene mutations in a pedigree with oculocutaneous albinism by using targeted next-generation sequencing technology. Methods Clinical data were collected from a pedigree with oculocutaneous albinism. Genomic DNA was extracted from peripheral blood cells of the proband and his parents. High-throughput sequencing technology was used for sequence analysis of coding regions in exons of 29 genes including TYR, OCA2, TYRP1 and SLC45A2 in the proband to find potential pathogenic gene mutations. Sanger sequencing was conducted to detect the corresponding genetic loci in the parents. Results Two heterozygous mutations were identified in the TYR gene of the proband, including a novel mutation c.534G 〉 C （p.Trp178Cys） and a known mutation c.1147G 〉 A （p.Asp383Asn）. The detection of the TYR gene mutations in the parents of the proband showed that the c.534G 〉 C and c.1147G 〉 A mutations in the proband were inherited from his father and mother respectively. Conclusion A novel pathogenic mutation c.534G 〉 C in the TYR gene is identified in the pedigree with oculocutaneous albinism by using targeted next-generation sequencing technology.