X连锁无脑回畸形伴异常生殖器患儿1例的ARX基因变异分析

Analysis of ARX gene variant in a child with X-linked lissencephaly with abnormal genitalia

目的对1例X连锁无脑回畸形伴异常生殖器(XLAG)患儿进行ARX基因变异及临床表征分析,以明确其遗传学病因。方法将2021年5月郑州大学第三附属医院收治的1例XLAG患儿进行全外显子组高通量测序,对候选变异进行Sanger测序家系检测。根据美国医学遗传学与基因组学学会(ACMG)相关指南,针对测序数据利用Anno变异位点注释解读软件和XYGeneRanger变异位点检测软件进行分析。结果该家系患儿检出ARX基因c.945_948del半合子变异,为第2外显子的移码变异,可能导致蛋白截短。患儿母亲携带该杂合变异,父亲为野生型,变异既往未见报道。结论ARX基因c.945_948del变异与患儿XLAG的发生相关。上述发现丰富了ARX基因的变异谱,为患儿的诊断及遗传咨询提供了依据。

ObjectiveTo explore the clinical characteristics and genetic basis for a child with X-linked lissencephaly with abnormal genitalia(XLAG).MethodsA child with XLAG who had presented at the Third Affiliated Hospital of Zhengzhou University in May 2021 was selected as the study subject.Peripheral blood samples of the child and his parents were collected and subjected to high-throughput sequencing.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the result was analyzed by using bioinformatic software.ResultsThe child was found to have harbored a hemizygous c.945_948del variant in exon 2 of the ARX gene,which as a frameshifting variant has resulted in a truncated protein.His mother was found to be heterozygous for the variant,whilst his father was of wild type.The variant was unreported previously.ConclusionThe hemizygous c.945_948del variant of the ARX gene probably underlay the XLAG in this patient.Above finding has provided a basis for the diagnosis and genetic counseling for this family.