先天性白内障家系的产前超声与致病基因研究  

Study on prenatal ultrasonograhy and pathogenic genes of congenital cataract pedigree

作　　者：刘珍[1] 曹洪瑞 王月 郭义雄 于萍[1] 李娜娜[1] 邓莹[1] 朱军[1] LIU Zhen;CAO Hong-Rui;WANG Yue(China Birth Defects Monitoring Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China)

机构地区：[1]四川大学华西第二医院中国出生缺陷监测中心,四川成都610041 [2]沧州市沧县医院门诊超声科,河北沧州061000 [3]沧州市沧县医院眼科,河北沧州061000

出　　处：《中国妇幼保健》2018年第14期3246-3249,共4页Maternal and Child Health Care of China

基　　金：国家十二五科技支撑项目(2014BAI06B01);科技基础性工作专项(2014FY110700)

摘　　要：目的分析先天性白内障家系的产前超声诊断情况和致病基因,为发现潜在基因突变位点和早诊早治提供科学依据。方法对1例先天性白内障先证者孕妇进行产前超声检查和病史调查,在其分娩后采集双胎脐血。经过完善的眼科学检查后,采集该大家系共19名成员(包括10名患者,9名非患者)血液样品,将患者与非患者进行全外显子组基因测序,筛选候选基因,对基因突变位点进行直接测序并在相关群体中进行验证。结果产前超声检查发现该患者分娩双胎均为先天性白内障患者,该家系为5代患病的先天性白内障常染色体显性遗传家族。经全外显子基因组测序,新发现SNP 2 553个,新发现Indel 3881个。经候选基因一代测序,验证发现家系内患者CRYGD基因第2外显子70位有1个C>A碱基的杂合突变(c.70C>A),并由此导致了蛋白第24位上脯氨酸被苏氨酸所取代(p.Pro24Thr),正常对照未见该点突变。结论 CRYGD基因的错义突变c.70C>A是该先天性白内障家系的致病原因。家系调查询问病史尤为重要,在孕期错过基因诊断的情况下,产前超声诊断为更有效的筛查手段。Objective To analyze prenatal ultrasonic diagnosis and pathogenic genes of congenital cataract pedigree,provide a scientific basis for detection of potential gene mutation sites,early diagnosis,and early treatment. Methods Prenatal ultrasonography and medical history investigation were performed in one pregnant woman of propositus of congenital cataract pedigree,the umbilical cord blood samples of twin after delivery were obtained,after complete ophthalmologic examination,the blood samples of 19 family members were collected,including 10 patients and 9 normal persons. A whole exome sequencing of 10 patients and 9 normal persons was used to identify candidate mutations. The candidate genes were sequenced and verified in the relevant population. Results Prenatal ultrasonography showed that the twin born by the propositus were found with congenital cataract pedigree,the pedigree was a five-generation cataract family with autosomal dominant inheritance of congenital cataract. Whole exome sequencing identified 2 553 new-found single nucleotide polymorphisms and 3 881 new-found indels. The sequencing of candidate genes showed that there was a heterozygous mutation of exon 2 in CRYGD gene（ c. 70 C〉A）,which induced p. Pro24 Thr,and the point mutation was not found in normal persons. Conclusion A missense mutation of CRYGD（ c. 70 C〉A） may be responsible for congenital cataract pedigree. Family history survey is particularly important during clinical examination.Prenatal ultrasonic diagnosis is a more effective screening means when missing genetic diagnosis during pregnancy.

关 键 词：先天性白内障 产前诊断 CRYGD基因 外显子组测序 产前超声 

分 类 号：R394[医药卫生—医学遗传学]