两例Mowat-Wilson综合征患者的ZEB2基因变异分析

Analysis of ZEB2 gene variation in two patients with Mowat-Wilson syndrome

目的:分析两例疑似Mowat-Wilson综合征(Mowat-Wilson syndrome,MWS)患儿的遗传学病因,帮助确诊并为家系遗传咨询提供依据。方法﹑采集2例无亲缘关系患儿及其家系成员静脉全血提取基因组DNA,应用家系全外显子组测序及基因组拷贝数变异测序进行变异检测,可疑变异位点利用Sanger测序对先证者及其家系成员进行验证。结果︰患儿1携带ZEB2基因c.2769C>A(p.Y923*)杂合变异,为新发变异,表型正常的父母和姐姐均未检测到。患儿2携带ZEB2基因c.315delC(p.A105Afs*3)杂合变异,为未报道过的新发变异,表型正常的父母未检测到。这两个变异均属于致病性变异,导致终止密码子提前出现。结论ZEB2基因c.2769C>A(p.Y923*)和c.315delC(p.A105Afs*3)变异可能分别是导致两例患儿MWS的病因,基因检测有助于明确诊断并为患儿家系的遗传咨询提供依据。

Objective To identify pathogenic variants in two patients with suspected for Mowat-Wilson syndrome(MWS).Methods Genomic DNA was extracted from peripheral blood samples of thepatients and his family members,and gene variants were analysis by Trio-whole exome sequences and copynumber variation sequencing.Results Patient 1 was found to carried a de novo heterozygous c.2769C>A(p.Y923*)nonsense variant of ZEB2 gene.The variant was not found in his healthy parents and sister,Patient 2 carried a de nowo heterozygous frameshift variant of the ZEB2 gene,namely c.315delC(p.A105Afs*3),which has not been reported previously.Both variants were predicted to be pathogenic andcan lead to premature occurrence of stop codons.Conclusion The heterozygous c.2769C>A(p.Y923*)and c.315delC(p.A105Afs*3)variants of the ZEB2 gene probably underlay the pathogenesis in the twopatients.Gene testing has facilitated confirmation of the diagnosis and genetic counselling.