Genetic analysis of two families with Short-rib thoracic dysplasia type 3
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目的 对2例疑似短肋胸廓发育不良的胎儿进行致病变异鉴定和临床分型。 方法 在获取知情同意后，对引产胎儿进行全面检查，记录其临床表型。用常规酚-氯仿法提取胎儿皮肤组织及其父母外周血样的基因组DNA，通过全外显子组测序(WES)对其进行检测，对候选致病性变异进行Sanger测序家系验证；用VarCards在线软件分析变异的致病性，结合Swiss-PdbViewer预测变异对蛋白质三级结构的影响。 结果 两例胎儿均携带DYNC2H1基因的复合杂合变异。胎儿1为c.515C>A(p.Pro172Gln)和c.5983G>A(p.Ala1995Thr)，胎儿2为c.5920G>T (p.Gly1974*)和c.9908T>C(p.Ile3303Thr)。两例胎儿的亲代均携带杂合变异。 结论 DYNC2H1基因的复合杂合变异很可能是两例胎儿的遗传学病因，二者均被确诊为SRTD3型。 Objective To explore the pathogenic variants and clinical classification of two fetuses with Short-rib thoracic dysplasia with or without polydactyly (SRTD). Methods With informed consent obtained, the phenotypic characteristics of the fetuses were comprehensively examined, and genomic DNA was extracted from fetal skin tissue and peripheral blood samples of the parents with conventional phenol-chloroform method. Whole exome sequencing (WES) was carried out on both fetuses, and the candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was analyzed using bioinformatic software VarCards, and the impact of the variants on the protein structure was predicted with Swiss-Pdb-viewer. Results Both fetuses were found to harbor compound heterozygous variants of the DYNC2H1 gene, including c. 515C>A (p.Pro172Gln) and c. 5983G>A (p.Ala1995Thr) in fetus 1, and c. 5920G>T(p.Gly1974*) and c. 9908T>C(p.Ile3303Thr) in fetus 2. The parents of both fetuses were heterozygous carriers. Conclusion The compound heterozygous variants of the DYNC2H1 gene probably underlay the SRTD3 in the two fetuses.
Objective To explore the pathogenic variants and clinical classification of two fetuses with Short-rib thoracic dysplasia with or without polydactyly (SRTD). Methods With informed consent obtained, the phenotypic characteristics of the fetuses were comprehensively examined, and genomic DNA was extracted from fetal skin tissue and peripheral blood samples of the parents with conventional phenol-chloroform method. Whole exome sequencing (WES) was carried out on both fetuses, and the candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was analyzed using bioinformatic software VarCards, and the impact of the variants on the protein structure was predicted with Swiss-Pdb-viewer. Results Both fetuses were found to harbor compound heterozygous variants of the DYNC2H1 gene, including c. 515C>A (p.Pro172Gln) and c. 5983G>A (p.Ala1995Thr) in fetus 1, and c. 5920G>T(p.Gly1974*) and c. 9908T>C(p.Ile3303Thr) in fetus 2. The parents of both fetuses were heterozygous carriers. Conclusion The compound heterozygous variants of the DYNC2H1 gene probably underlay the SRTD3 in the two fetuses.
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