应用全外显子测序对5例白化病家系遗传病因分析及产前诊断  

Genetic etiology and prenatal diagnosis of five albinism families by whole exon sequencing.

作　　者：徐盈 石润茜 郭芬芬 张建芳 黎昱 宋婷婷 郑娇 沈宇杰 李远凤 党颖慧 杨红 Xu Ying;Shi Runqian;Guo Fenfen(Department of Obstetrics and Gynecology,the First Affiliated Hospital of Air Force Medical University,Xi'an 710032)

机构地区：[1]中国人民解放军空军军医大学第一附属医院妇产科,西安710032

出　　处：《现代妇产科进展》2023年第11期801-805,共5页Progress in Obstetrics and Gynecology

基　　金：西安市科技计划项目(No:20YXYJ0009-7);陕西省自然科学基础研究计划(No:2022JQ-977);陕西省重点研发计划(No:2019ZDLSF01-06);国家自然科学基金项目资助(No:82172993)。

摘　　要：目的:研究5例具有白化病家族史的家系病因、胎儿的产前诊断和妊娠结局,并评价全外显子测序在白化病家系致病基因鉴定中的临床价值。方法:采用全外显子测序技术结合Sanger测序鉴定5例具有白化病家系受检者基因型,进一步采用绒毛活检术/羊膜腔穿刺技术获取胎儿标本,进行产前基因诊断。结果:家系1在TYR基因发现变异位点c.1184G>A和c.929dupC,家系2在TYR基因存在致病变异c.929dupC和c.61C>T,家系3在TYR基因存在致病变异位点c.1112_1113delAT和c.929dupC,家系4在OCA2基因上存在c.1001C>T和c.2051T>G变异,家系5在HPS1基因上存在变异位点c.972dupC和c.1932delC。对2例胎儿进行产前诊断,1例为白化病携带者,1例基因型正常,出生后随访临床表型未见异常。结论:全外显子测序技术可全面、精准地鉴定白化病家系的致病因素,对有再生育需求的家庭起到优生优育指导作用,具有重要的临床意义。Objective:To investigate the family etiology,prenatal diagnosis and pregnancy outcome of five albinism families,and to evaluate the clinical value of whole exon sequencing in the identification of pathogenic genes in albinism families.Methods:Whole exon sequencing technology combined with Sanger sequencing was used to identify the genotypes of five patients with albinism.Fetal specimens were obtained by villus biopsy/amniocentesis for prenatal families genetic diagnosis.Results:c.1184G>A and c.929dupC variants of TYR gene were found in family 1;Family 2 had pathogenic variants in TYR gene c.929dupC and c.61C>T;Family 3 had pathogenic variants c.1112_1113delAT and c.929dupC;Family 4 had variants in OCA2 gene c.1001C>T and c.2051T>G.There were variants c.972dupC and c.1932delC on HPS1 gene in family 5.In addition,the prenatal diagnosis of 2 fetuses was performed:1 was a carrier of albinism,and 1 was a normal genotype.No abnormal clinical phenotype was observed during post-natal follow-up.Conclusion:Whole exon sequencing can compre-hensively and accurately identify the pathogenic factors of albinism families,and play an important role in guiding the birth and fertility of families with reproductive needs,which has important clinical significance.

关 键 词：白化病 基因诊断 全外显子测序 Sanger测序 致病性评估 

分 类 号：R715.5[医药卫生—妇产科学]