WDR62基因变异致原发性小头畸形1例  

A case of primary microcephaly associated with compound heterozygous variants of WDR62 gene

作　　者：余丽华[1] 王兴旺 刘玲[1] 曾玉坤[1] 齐一鸣[1] 黄演林[1] 丁红珂[1] Yu Lihua;Wang Xingwang;Liu Ling;Zeng Yukun;Qi Yiming;Huang Yanlin;Ding Hongke(Medical Genetics Center of Guangdong Maternal and Child Health Care Hospital,Guangzhou,Guangdong 511442,China)

机构地区：[1]广东省妇幼保健院医学遗传中心,广州511442

出　　处：《中华医学遗传学杂志》2025年第2期175-179,共5页Chinese Journal of Medical Genetics

基　　金：广东省医学科学技术研究基金(A2020302、B2021258);广东省科技计划(2021A1414020008)。

摘　　要：目的对1例原发性小头畸形、生长发育落后的患儿进行基因变异分析。方法以1例因发育落后于2020年10月来广东省妇幼保健院就诊的女性患儿作为研究对象。采集患儿及其父母的外周血样,对其进行全外显子组测序检测,并用Sanger测序对候选变异进行家系验证。本研究通过了广东省妇幼保健院医学伦理委员会的审查(批准号:202201278)。结果基因检测发现患儿携带WDR62基因c.2963delC(p.Pro988Argfs*80)和c.3163G>T(p.Glu1055*)复合杂合变异,分别来源于其父亲和母亲。前者位于第24外显子,为缺失移码变异,后者位于第26外显子,为无义变异,均可能导致蛋白质翻译提前终止。根据美国医学遗传学和基因组学学会(ACMG)相关指南均评级为可能致病性。结论结合患儿的临床表现、变异位点的致病性及家系分析,判断上述变异为患儿的遗传学病因。上述发现丰富了常染色体隐性遗传性原发性小头畸形2型的突变谱,也为该家系再次妊娠的产前诊断提供了线索。ObjectiveTo explore the genetic basis for a girl with primary microcephaly and growth retardation.MethodsA girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject.Peripheral blood samples were collected from the child and her parents.Trio whole exome sequencing was carried out,and candidate variants were verified by Sanger sequencing and bioinformatic analysis.This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital(Ethics No.202201278).ResultsDNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene,including a frameshifting c.2963delC(p.Pro988Argfs*80)variant in exon 24 which was inherited from the unaffected father,and a nonsense c.3163G>T(p.Glu1055*)variant in exon 26,which was inherited from her unaffected mother.Both variants were predicted to affect the reading frame of the WDR62 gene.ConclusionBased on the clinical manifestations,results of genetic testing and pedigree analysis,the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child.Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2,and facilitated genetic counseling for the family.

关 键 词：原发性小头畸形2型 生长发育落后 WDR62基因 变异 

分 类 号：R725.9[医药卫生—儿科]