ASPM基因变异所致的常染色体隐性遗传原发性小头畸形5型家系的诊断及遗传咨询  

Diagnosis and counseling for a Chinese pedigree affected with autosomal recessive primary microcephaly 5 due to variants of ASPM gene

作　　者：张艳[1] 曾丽娜[1] 林荔[1] Zhang Yan;Zeng Lina;Lin Li(Center of Prenatal Diagnosis,The Affiliated Hospital of Putian College,Putian,Fujian 351100,China)

机构地区：[1]莆田学院附属医院产前诊断中心,莆田351100

出　　处：《中华医学遗传学杂志》2022年第4期405-408,共4页Chinese Journal of Medical Genetics

基　　金：莆田学院2019年校内科研项目(2019099)。

摘　　要：目的对一个常染色体隐性遗传原发性小头畸形5型(autosomal recessive primary microcephaly 5,MCPH5)家系进行ASPM致病基因突变位点分析,进一步为家系提供遗传咨询及产前诊断。方法采集先证者及其父母的外周血,以及胎儿的羊水细胞,提取基因组DNA,通过PCR-Sanger测序对先证者ASPM基因的外显子及外显子/内含子衔接区进行序列分析,并在其家系中进行变异验证。结果先证者存在ASPM基因第18外显子c.8214dupT(p.Q2739fs)和第23外显子c.9541C>T(p.R3181X)复合杂合突变,分别来自其父亲及母亲;本次妊娠胎儿羊水细胞染色体核型与SNP Array检测均未见异常,胎儿携带ASPM基因第23外显子c.9541C>T(p.R3181X)杂合突变,出生后表型正常。结论ASPM基因c.8214dupT(p.Q2739fs)与c.9541C>T(p.R3181X)复合杂合突变为常染色体隐性遗传原发性小头畸形5型的致病基因,本研究结果为该家系行遗传咨询与产前诊断提供了依据。Objective To detect potential mutation of the ASPM gene in a Chinese pedigree affected with autosomal recessive primary microcephaly 5(MCPH5).Methods Peripheral venous blood samples were collected from the proband and her parents.Amniotic fluid sample was also collected upon her mother’s subsequent pregnancy.Following extraction of genomic DNA,PCR and Sanger sequencing were carried out to identify potential variants of the ASPM gene.Results The proband was found to harbor compound heterozygous variants of the ASPM gene,namely c.8214dupT(p.Q2739fs)in exon 18 and c.9541C>T(p.R3181X)in exon 23,which were respectively inherited from her father and mother.The fetus has found to have inherited the c.9541C>T(p.R3181X)variant only.Conclusion The c.8214dupT(p.Q2739fs)and c.9541C>T(p.R3181X)compound heterozygous variants of the ASPM gene probably underlay the pathogenesis of MCPH5 in this patient.Above finding has enabled genetic counseling and prenatal diagnosis for her family.

关 键 词：常染色体隐性遗传原发性小头畸形 ASPM基因 产前基因诊断 遗传咨询 

分 类 号：R725.9[医药卫生—儿科]