1个DYNC2H1基因变异导致的短肋多指综合征Ⅲ型家系的遗传学分析  

Genetic analysis of a pedigree of DYNC2H1 gene variation-caused short rib polydactyly syndrome typeⅢ

作　　者：王俊霞[1] 王方娜[2] 李娟[2] 石子佳 程青青 郑宗朋 楚伟[2] 高健[2] Junxia Wang;Fangna Wang;Juan Li;Zijia Shi;Qingqing Cheng;Zongpeng Zheng;Wei Chu;Jian Gao(Graduate School,Hebei Medical University,Shijiazhuang 050017,China;Department of Reproduction and Genetics,Hebei General Hospital,Shijiazhuang 050051,China;Graduate School,Hebei North University,Zhangjiakou 075000,China)

机构地区：[1]河北医科大学研究生院,石家庄050017 [2]河北省人民医院生殖遗传科,石家庄050051 [3]河北北方学院研究生院,张家口075000

出　　处：《中华围产医学杂志》2022年第4期290-293,共4页Chinese Journal of Perinatal Medicine

摘　　要：本文报道1个连续3次妊娠早孕期超声均提示胎儿四肢短小家系的遗传学分析。取第2次妊娠引产胎儿组织行染色体核型分析及全外显子组测序,结果提示DYNC2H1基因存在EX64-EX83 Del及c.8190G>T杂合变异。实时荧光定量聚合酶链反应及Sanger测序验证2个变异分别遗传自表型正常的父亲和母亲,前者为疑似致病性变异,后者为临床意义未明变异。综合病史及变异基因特点,高度怀疑胎儿为常染色体隐性遗传的复合杂合变异导致的短肋多指综合征Ⅲ型。第3次妊娠胎儿引产后采用实时荧光定量聚合酶链反应和Sanger测序进行验证,结果与第2次妊娠胎儿一致。由于第2、3次妊娠胎儿表型相似,提示DYNC2H1基因EX64-EX83 Del及c.8190G>T杂合变异可能是该家系短肋多指综合征Ⅲ型的致病变异。This paper reported the genetic analysis of a pedigree in which three affected fetuses with short limbs were revealed by first-trimester ultrasonography in three consecutive pregnancies.Tissues of the second aborted fetus were collected and analyzed by chromosome karyotype analysis and whole exome sequencing.The results indicated compound heterozygous mutations of EX64-EX83 Del and c.8190G>T in the DYNC2H1 gene.Real-time fluorescence quantitative polymerase chain reaction and Sanger sequencing further confirmed that the two variants were inherited from the father and the mother with normal phenotypes,respectively.EX64-EX83 Del was a likely pathogenic variant and c.8190G>T was a variant of uncertain significance.Based on the above results and the medical history,it was highly suspected that the fetus had autosomal recessive short rib polydactyly syndrome typeⅢcaused by compound heterozygous variants.Real-time fluorescent quantitative polymerase chain reaction and Sanger sequencing results of the third aborted fetus were consistent with the second fetus.Given the same phenotypes of fetuses in the second and third pregnancy,it was strongly suggested that the heterozygous variations of EX64-EX83 Del and c.8190G>T in the DYNC2H1 gene were the pathogenic variants in this pedigree.

关 键 词：短肋多指(趾)畸形综合征 胞浆动力蛋白类 骨软骨发育不良 肋骨 杂合子 遗传变异 全外显子组测序 

分 类 号：R174.5[医药卫生—妇幼卫生保健] R440[医药卫生—公共卫生与预防医学]