摘要目的:探讨1家系中2例 BCL11A相关智力障碍( BCL11A-ID)患者的遗传学病因。 方法:选取2020年6月19日，于临沂市人民医院遗传咨询门诊就诊的1个 BCL11A-ID家系为研究对象。分析先证者及家系成员的临床资料，并进行染色体核型分析、家系全外显子组测序(trio-WES)、拷贝数变异测序(CNV-seq)，可疑变异经Sanger测序验证并进行致病性评估。 结果:先证者及其母亲表现为智力障碍及语言发育迟缓，二者的胎儿血红蛋白(HbF)显著升高。WES发现先证者 BCL11A基因第4外显子存在c.1327_c.1328delTC(p.Ser443Hisfs*128)杂合变异，导致编码蛋白截短表达，Sanger测序验证该变异遗传自母亲。检索相关数据库未见报道，为新变异。根据美国医学遗传学与基因组学学会(ACMG)指南判定为致病性变异(PVS1+PM2+PP1)。先证者及其父母、哥哥的染色体核型分析未见异常，先证者及其父母的CNV-seq未见异常。 结论:本研究确诊了先证者及其母亲为 BCL11A-ID患者，c.1327_c.1328delTC(p.Ser443Hisfs*128)变异可能是该病的致病原因，丰富了 BCL11A基因的变异谱。

abstractsObjective:To explore the genetic basis for two patients from a family with BCL11A-related intellectual disability ( BCL11A-ID). Methods:Clinical data of the proband and her family members was analyzed. Chromosomal karyotyping analysis, trio-whole exome sequencing (trio-WES) and copy number variation sequencing (CNV-seq) were carried out. For the suspected genetic variants, Sanger sequencing was used to verify, and pathogenicity assessment was conducted.Results:The proband and her mother both had intellectual and language impairment, and their fetal hemoglobin (HbF) was significantly elevated. A heterozygous c. 1327_c.1328delTC (p.Ser443Hisfs*128) variant was found in exon 4 of the BCL11A gene by WES, which has resulted in truncated expression of the encoded protein, and Sanger sequencing has verified that the variant was inherited from the mother. The variant was not found in related databases. The variant was predicted as a pathogenic variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG) (PVS1+ PM2+ PP1). No karyotypic abnormality was found in the proband, her parents and brother, and no pathogenic CNVs were found in the proband and her parents. Conclusion:The c. 1327_c.1328delTC (p.Ser443Hisfs*128) variant may underlay the BCL11A-ID in the proband and her mother. This de novo variant has expanded the mutational spectrum of the BCL11A gene.