新发杂合Ser249Cys变异导致的骨发育不良家系分析  

Pedigree Analysis of Skeletal Dysplasia Caused by a Novel Heterozygous Ser249Cys Variants

作　　者：李杨 狄华[1] 严凯 李慧娟 穆艳超 LI Yang;DI Hua;YAN Kai;LI Hui-juan;MU Yan-chao(Prenatal Diagnosis Center,Anyang Maternal and Child Health Care Hospital,Anyang Key Laboratory of Prenatal Diagnosis,Anyang 455000,Henan Province,China)

机构地区：[1]安阳市妇幼保健院产前诊断中心,安阳市产前诊断重点实验室,河南安阳455000

出　　处：《罕少疾病杂志》2025年第3期6-7,共2页Journal of Rare and Uncommon Diseases

基　　金：安阳市重点研发与推广专项:低深度测序技术在预防出生缺陷中的应用(2023C01SF156)。

摘　　要：目的 对一个超声诊断四肢短小畸形伴致死性骨发育不良可能家系进行FGFR3基因突变分析和调查。方法 采集胎儿组织与胎儿父母血液标本,进行高通量测序,采用Sanger测序对变异进行验证。使用多种数据库对检测结果进行分析。结果 胎儿存在FGFR3 c.746CG(p.Ser249Cys)杂合错义变异,胎儿父母FGFR3基因均为野生型;胎儿和父母样本均未检测到100kb以上已知明确致病的拷贝数变异。结论 胎儿所具有的FGFR3 c.746CG (p.Ser249Cys)杂合错义变异为新发变异,是造成骨发育不良的原因。新发基因变异的检出丰富了遗传性骨发育不良的致病机制。Objective To analyze and investigate the mutation of FGFR3 gene in a possible family diagnosed by ultrasound with short limbs and fatal osteopathy.Methods Fetal tissue and fetal parents'blood samples were collected for high-throughput sequencing,and Sanger sequencing was used to verify the variation.The test results were analyzed using a variety of databases.Results There was FGFR3 c.746CG(p.Ser249Cys)heterozygous missense mutation in the fetus,and the FGFR3 gene in both fetal parents was wild type.Both fetal and parental samples had not been detected copy number variants over 100kb known to be clearly pathogenic.Conclusion FGFR3 c.746CG(p.Ser249Cys)heterozygous mutation in fetuses is a new mutation,which may be the cause of skeletal dysplasia.The detection of new gene variants has enriched the pathogenesis of hereditary skeletal dysplasia.

关 键 词：FGFR3 骨发育不良 畸形 家系 

分 类 号：R394.3[医药卫生—医学遗传学]