一例脑桥小脑发育不全6型胎儿的RARS2基因变异分析

Analysis of genetic variant in a fetus featuring pontocerebellar hypoplasia type 6

目的对1例小脑发育不良、侧脑室增宽引产胎儿进行基因变异检测,明确其可能的致病原因。方法获取引产胎儿皮肤组织标本和其父母的外周血样本,对胎儿进行全外显子组测序,应用PCR及Sanger测序对可疑致病位点进行验证。结果产前超声提示胎儿NT增厚(0.4 cm)和侧脑室增宽,磁共振显示胎儿幕下脑发育不良。全外显子组测序结果显示胎儿RARS2基因存在c.1A>G和c.1564G>A复合杂合变异,其中c.1A>G变异为已知致病性变异,c.1564G>A为尚未报道过的变异,分别遗传自父母。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南,c.1564G>A变异为可能致病性变异(PM2+PM3+PP3+PP4)。结论RARS2基因的c.1A>G和c.1564G>A复合杂合变异可能是患儿的致病原因,新变异的检出丰富了RARS2基因的变异谱。

Objective To explore the genetic basis for a fetus with cerebellar dysplasia and widened lateral ventricles.Methods The couple have elected induced abortion after careful counseling.Skin tissue sample from the abortus and peripheral venous blood samples from both parents were collected for the extraction of genomic DNA,which was then subjected to whole exome sequencing.Candidate variant was verified by Sanger sequencing.Results Prenatal ultrasonography showed increased nuchal translucency(0.4 cm)and widened lateral ventricles.Magnetic resonance imaging revealed infratentorial brain dysplasia.By DNA sequencing,the fetus was found to carry compound heterozygous variants c.1A>G and c.1564G>A of the RARS2 gene,which were inherited from its father and mother,respectively.Among these,c.1A>G was known to be pathogenic,but the pathogenicity of c.1564G>A was unreported previously.Based on the American College of Medical Genetics and Genomics guidelines,the c.1564G>A variant of RARS2 gene was predicted to be likely pathogenic(PM2+PM3+PP3+PP4).Conclusion The compound heterozygous variants c.1A>G and c.1564G>A of the RARS2 gene contributed to the fetus suffering from pontocerebellar hypoplasia type 6,which expanded variant spectrum of RARS2 gene.