一个L1CAM基因新变异导致的HSAS综合征的家系分析

Analysis of a pedigree affected with HSAS syndrome due to a noval variant of L1CAM gene

目的对1个HSAS综合征家系L1CAM基因进行变异分析,明确该家系脑积水胎儿的致病原因,为家系的遗传咨询和产前诊断提供依据。方法收集孕中期经超声发现胎儿脑积水引产儿的DNA,进行全外显子测序,并用Sanger测序对疑似致病变异进行家系验证。结果胎儿L1CAM基因(OMIM*308840)存在c.620A>G(p.Tyr207Cys)半合子变异,胎儿姐姐与母亲携带c.620A>G(p.Tyr207Cys)杂合变异,其父亲、外祖父母、舅舅该位点均为野生型。依据美国医学遗传学与基因组学学会变异分类标准与指南,该变异为可能致病变异(PM1+PM2+PP3+PP4)。结论L1CAM基因的c.620A>G半合子变异很可能是该家系胎儿的致病原因。

Objective To explore the genetic basis for a fetus with hydrocephalus.Methods The fetus was found to have hydrocephalus upon ultrasonography duringthe second trimester.Following induced abortion,fetal tissue was collected for the extraction of DNA and whole exome sequencing.Sanger sequencing was used to verify the suspected variants in the family.Results The fetus was found to harbor a hemizygous c.620A>G(p.Tyr207Cys)variantof the L1CAM gene(OMIM 308840),for which his mother and sister were heterozygous carriers.The same variant was not found in his father,uncle and grandparents.Based on the standards and guidelines of the American College of Medical Genetics and Genomics,the variant was predicted to be likely pathogenic(PM1+PM2+PP3+PP4).Conclusion The hemizygous c.620A>G(p.Tyr207Cys)variant of the L1CAM gene probably underlay the hydrocephalus in this fetus.