短肋多指综合征3型2个家系的DYNC2H1基因检测及产前诊断  

DYNC2H1 gene mutation analysis and prenatal diagnosis in two pedigrees affected with short rib-polydactyly syndrome typeⅢ

作　　者：孙玥 刘宁[1] 李倩倩[1] 焦智慧[1] 孔祥东[1] 白莹[1] Sun Yue;Liu Ning;Li Qianqian;Jiao Zhihui;Kong Xiangdong;Bai Ying(Genetic and Prenatal Diagnosis Center,Department of Obstetrics and Gynecology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院妇产医学部遗传与产前诊断中心,郑州450052

出　　处：《中华围产医学杂志》2022年第1期48-52,共5页Chinese Journal of Perinatal Medicine

基　　金：国家自然科学基金青年科学基金(81501851);河南省医学科技攻关计划(201702003)。

摘　　要：目的对2例短肋多指综合征3型(short rib polydactyly syndrome typeⅢ,SRPSⅢ)的胎儿进行产前诊断,明确其发病的分子遗传学病因。方法应用二代测序技术(next generation sequencing,NGS)对2015年8月和2020年6月于郑州大学第一附属医院就诊的2个患病胎儿(先证者)进行遗传性骨病226个相关致病基因检测。发现可疑致病位点后,对家系成员进行Sanger双向测序验证分析。确定致病变异后,对家系1的高危胎儿进行产前诊断。结果2个SRPSⅢ家系均发现了DYNC2H1基因变异,其中家系1先证者携带DYNC2H1基因c.5881A>G(p.Lys1961Glu)纯合变异,父母分别为携带者;家系2先证者DYNC2H1基因存在c.10606C>T(p.Arg3536*)和c.8954T>G(p.Val2985Gly)复合杂合变异,分别来自父亲和母亲。2个家系均符合常染色体隐性遗传,DYNC2H1基因c.5881A>G(p.Lys1961Glu)、c.8954T>G(p.Val2985Gly)为首次报道的疑似致病性变异。产前诊断结果显示家系1胎儿(Ⅱ-7)未见DYNC2H1基因c.5881A>G(p.Lys1961Glu)变异,孕妇选择继续妊娠,分娩后取脐带血行基因检测,结果与产前基因诊断结果一致。结论DYNC2H1基因变异是这2个家系的致病原因。Objective To investigate the molecular genetic etiology of two fetuses with short rib-polydactyly syndrome typeⅢ(SRPSⅢ).Methods Next-generation sequencing(NGS)was used to detect 226 known genes related to inherited skeletal dysplasia in two fetuses with SRPSⅢdiagnosed in the First Affiliated Hospital of Zhengzhou University in August 2015 and June 2020.Suspect pathological variants were verified in the pedigree members using Sanger sequencing.The prenatal genetic diagnosis of the high-risk fetus in pedigree one was conducted to identify the confirmed pathogenic variation.Results The homozygous mutation of DYNC2H1 gene c.5881A>G(p.Lys1961Glu)was identified in the proband in pedigree one,and the parents were the carriers.The proband in pedigree two carried compound heterozygous mutations in the DYNC2H1 gene with c.10606C>T(p.Arg3536*)inherited from the father and c.8954T>G(p.Val2985Gly)from the mother.Autosomal recessive inheritance was confirmed in both pedigrees.Mutations of c.5881A>G(p.Lys1961Glu)and c.8954T>G(p.Val2985Gly)in the DYNC2H1 gene were likely pathogenic variants and had not been reported before.The prenatal diagnosis did not identify the DYNC2H1 gene c.5881A>G(p.Lys1961Glu)mutation in the fetus(Ⅱ-7)in pedigree one,which was confirmed by the umbilical cord blood sample after birth.Conclusion DYNC2H1 gene mutation underlies the fetal skeletal dysplasia in the two pedigrees.

关 键 词：短肋多指(趾)畸形综合征 系谱 胞浆动力蛋白类 高通量核苷酸序列分析 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]