摘要目的:分析1例智力障碍、语言发育滞后患儿的遗传学病因，并为其家系提供遗传咨询及产前诊断。方法:收集患儿的临床资料，采集患儿及其家系成员的外周血样，提取DNA，进行全外显子组测序，对候选变异进行Sanger测序验证，并对高危胎儿进行产前诊断。结果:患儿主要表现为智力障碍、语言发育滞后、睑下垂、斜视、畏光、多动和脾气暴躁等。全外显子组测序结果显示患儿存在 KAT6A基因c.5314dupA(p.Ser1772fs*20)致病性杂合变异，其父母均为野生型，诊断患儿为Arboleda-Tham综合征。另外患儿还存在 AIFM1基因c.56T>G(p.Leu19Trp)半合子变异，其母亲为杂合变异，表型正常的外祖父为半合子变异，可排除其致病性。高危胎儿未携带 KAT6A基因c.5314dupA变异。 结论:KAT6A基因c.5314dupA(Ser1772fs*20)杂合变异可能是患儿的致病原因，基因检测为该家系的遗传咨询及产前诊断提供了依据。

abstractsObjective:To explore the genetic etiology for a child featuring mental retardation and speech delay.Methods:Clinical data of the child was collected. DNA was extracted from peripheral blood samples of the child and members of his pedigree. Whole exome sequencing was carried out for the child, and candidate variants were verified by Sanger sequencing. Prenatal diagnosis was provided for his mother upon her subsequent pregnancy.Results:The child has mainly featured mental retardation, speech delay, ptosis, strabismus, photophobia, hyperactivity, and irritability. Whole exome sequencing revealed that he has harbored a pathogenic heterozygous variant of the KAT6A gene, namely c. 5314dupA (p.Ser1772fs*20), which was not detected in either of his parents. The child was diagnosed with Arboleda-Tham syndrome. The child was also found to harbor a hemizygous c. 56T>G (p.Leu19Trp) variant of the AIFM1 gene, for which his mother was heterozygous and his phenotypically normal maternal grandfather was hemizygous. Pathogenicity was excluded. Prenatal diagnosis has excluded the c. 5314dupA variant of the KAT6A gene in the fetus. Conclusion:The heterozygous c. 5314dupA (p.Ser1772fs*20) variant of the KAT6A gene probably underlay the Arboleda-Tham syndrome in this child. Above finding has enabled genetic counseling and prenatal diagnosis for this pedigree.