一例DYNC2H1变异所致短肋胸廓发育不良3型患儿的家系分析

Family analysis of a child with Short-rib polydactyly syndrome type Ⅲ due to variant of DYNC2H1 gene

目的对一例短肋多指综合征3型(short-rib polydactyly syndrome typeⅢ,SRPSⅢ)家系进行临床特征描述及相关致病基因变异分析,探讨其发病的分子遗传学病因,为评估其家庭的再发风险提供依据。方法采集第3胎引产组织,及引产胎儿的父母,祖父母,外祖父母的外周血,采用二代测序(next generation sequencing,NGS)方法进行全外显子测序(whole exome sequencing,WES),检出疑似致病变异后再结合Sanger测序,在家系内进行验证。结果检测到先证者DYNC2H1(NM_001080463.1)基因上携带母源性c.9819+1G>A变异和父源性c.4625C>A变异,Sanger测序技术验证了该家系符合常染色体隐性遗传的规律。结论DYNC2H1的c.9819+1G>A和c.4625C>A变异可能是导致该短肋多指综合征3型的致病原因。

Objective To report on the clinical characteristics of a family of short-rib polydactyly syndrome typeⅢand its pathogenic variants.Methods Muscle samples from the the third fetus was collected after the induction of labor,and peripheral blood samples of its parents and grandparents were also collected.Whole exome sequencing(WES)was carried out for the pedigree.Candidate variants were verified by Sanger sequencing of the family.Results The proband was found to harbor a c.9819+1G>A variant and a c.4625C>A variant of the DYNC2H1 gene,which were respectively inherited from its mother and father.Sanger sequencing verified that the family has fit the autosomal recessive inheritance.Conclusion The c.9819+1G>A and c.4625C>A variants of the DYNC2H1 gene probably underlay the short-rib polydactyly syndrome type 3 in the proband.