1例COL2A1基因新发变异致胎儿短肢畸形的遗传学分析

Genetic analysis of a case of fetal short limb deformity caused by a novel de novo mutation of COL2A1 gene

目的 对1例超声提示短肢畸形的引产胎儿进行基因测序分析,明确其遗传学病因。方法 提取引产胎儿肌肉组织基因组DNA,进行全基因组拷贝数变异检测和全外显子组测序分析,对检测到的可疑位点用Sanger测序进行验证,根据基于ACMG/AMP和ClinGen框架的遗传变异解读规则判断致病性。结果 引产胎儿的COL2A1基因存在c.3604_3606del杂合变异,父母均为野生型,该变异为新发变异,判定为“可疑致病”。结论 COL2A1基因的c.3604_3606del杂合变异为与胎儿短肢畸形相关的全新突变,该变异丰富了COL2A1基因变异谱。

Objective To explore genetic basis for an induced labor fetus with short limb deformity,gene sequencing analysis was performed.Methods Genomic DNA of muscle tissue from induced labor fetus was extracted and subjected to copy number variation sequencing and whole exome sequencing.Suspected variants were confirmed by Sanger sequencing.The pathogenicity was determined according to genetic variation interpretation rules based on ACMG/AMP and ClinGen framework.Results There was a c.3604_3606del heterozygous variation in COL2A1 gene in the induced labor fetus,while both parents were the wild type.This de novo mutation was judged to be “likely pathogenic”.Conclusion The c.3604_3606del heterozygous variation of COL2A1 gene is a novel mutation associated with fetal short limb deformity.This finding has enriched the spectrum of COL2A1 gene variants.