Xq25微重复智力障碍家系遗传学分析及产前诊断  

Genetic analysis and prenatal diagnosis of intellectual disability caused by Xq25 microduplication in a pedigree

作　　者：高越 吴东 肖海 王红丹 张梦汀 张倩 王凤阳 刘红彦 廖世秀 Gao Yue;Wu Dong;Xiao Hai;Wang Hongdan;Zhang Mengting;Zhang Qian;Wang Fengyang;Liu Hongyan;Liao Shixiu(Institute of Medical Genetics of Henan Provincial People's Hospital(People's Hospital of Zhengzhou University),Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院(郑州大学人民医院)医学遗传研究所,河南省遗传性疾病功能基因组重点实验室,郑州450003

出　　处：《中华围产医学杂志》2022年第12期949-953,共5页Chinese Journal of Perinatal Medicine

基　　金：河南省科技攻关项目(212102310046);河南省医学科技攻关项目(SBGJ202003001)。

摘　　要：目的:对1例27岁的智力障碍患者及其家系进行临床表现和遗传学分析,为家系提供遗传咨询和产前诊断。方法:采用常规染色体核型分析G显带和微阵列比较基因组杂交(array comparative genomic hybridization,aCGH)技术分析先证者(Ⅲ-1)及家系成员的染色体核型和全基因组拷贝数变异(copy number variation,CNV),并指导家系中孕妇(先证者之妹,Ⅲ-2)进行产前诊断。结果:G显带结果显示,该家系成员染色体核型均未见异常。aCGH结果显示先证者(Ⅲ-1)及先证者母亲(Ⅱ-3)、二舅(Ⅱ-2)、妹妹(Ⅲ-2)的X染色体q25区域存在1533 kb重复,CNV为致病性。Ⅲ-1与Ⅱ-2临床表型为智力障碍、言语不清、特殊面容;Ⅱ-3与Ⅲ-2无异常表型。Ⅲ-2羊水核型和aCGH未见异常,选择继续妊娠,足月阴道分娩1男性新生儿(Ⅳ-1)。随访至2022年2月,Ⅳ-1已3岁10个月,于幼儿园就学,体格、智力发育未见明显异常。结论:Xq25微重复可能是该家系中先证者出现智力障碍的原因,STAG2可能为Xq25区域关键基因。Objective To analyze the clinical and genetic characteristics of a 27-year-old male patient with intellectual disability and his pedigree to provide a reference for genetic counseling and prenatal diagnosis.Methods G-banding and array comparative genomic hybridization(aCGH)were performed to analyze the karyotypes and genomic copy number variations of the proband(Ⅲ-1)and his family members.Based on the results,prenatal diagnosis was performed for one pregnant woman(Ⅲ-2)in the pedigree who is the sister of the proband.Results All karyotyping were normal in the family members,while aCGH results showed a 1533 kb microduplication in the Xq25 region of the proband,his mother(Ⅱ-3),his uncle(Ⅱ-2),and his sister(Ⅲ-2),which was confirmed to be pathogenic.The proband and his uncle presented with intellectual disability,bradylalia,and facial dysmorphism.In contrast,his mother and sister showed normal phenotypes.His sister's fetal karyotype and aCGH results were normal,and the pregnancy continued.A male baby(Ⅳ-1)was delivered vaginally at term and showed no physical or intellectual abnormalities during a 46-month follow-up.Conclusions Xq25 microduplication might be the cause of intellectual disability in the proband.STAG2 is probably the essential gene in Xq25 region.

关 键 词：智力障碍 性染色体畸变 三体性 染色体 人 X 比较基因组杂交 产前诊断 

分 类 号：R714.5[医药卫生—妇产科学] R440[医药卫生—临床医学]