PIGW基因纯合变异致发育障碍合并癫痫发作患儿1例的遗传学分析

Genetic analysis of a child with developmental disorder and epilepsy due to a homozygous variant of PIGW gene

目的探讨1例发育障碍合并癫痫发作患儿的遗传学病因。方法选取2022年7月于广州市妇女儿童医疗中心神经内科就诊的1例发育障碍合并癫痫发作患儿为研究对象。回顾性分析患儿相关临床资料,对患儿进行全外显子组测序(WES),对候选变异进行Sanger测序验证与致病性分析。结果患儿为3岁女性,壮族人,主要表现为发育障碍合并癫痫发作,康复治疗无效。WES显示患儿携带PIGW基因c.821T>C(p.Leu274Pro)纯合错义变异,Sanger测序证实患儿父母与姐姐均携带PIGW基因c.821T>C(p.Leu274Pro)杂合错义变异,提示该变异遗传自父母。根据ACMG相关指南,该变异被评定为临床意义不明。结论PIGW基因c.821T>C(p.Leu274Pro)纯合变异可能是本研究患儿的遗传学病因,进一步丰富了PIGW基因变异谱。

Objective To explore the genetic basis for a child featuring global developmental disorder with epilepsy.Methods A child who had presented at Guangzhou Women and Children′s Medical Center in July 2022 was selected as the study subject.Clinical data was collected.Potential variant was detected by whole exome sequencing(WES).Candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results The child,a three-year-old ethnic Zhuang Chinese girl,had presented with global developmental disorder and epilepsy,for which rehabilitation therapy was ineffective.Genetic testing revealed that she has harbored a homozygous c.821T>C(p.Leu274Pro)missense variant of the PIGW gene,for which both of her parents and sister were heterozygous carriers.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the variant was classified as variant of uncertain significance.Conclusion The homozygous c.821T>C(p.Leu274Pro)variant of the PIGW gene probably underlay the onset of disease in this child.Above finding has enriched the mutational spectrum of the PIGW gene.