一个先天性眼外肌纤维化综合征家系的致病基因定位研究

Genetic Analysis in a Chinese Family with Congenital Fibrosis of Extraocular Muscle

目的:对一个常染色体显性遗传的先天性眼外肌纤维化(CFEOM)家系进行临床表型与突变基因研究。方法:纳入家系成员为研究对象:知情同意后进行眼科临床检查和采集外周血,提取DNA;根据已知遗传学突变位点,进行直接测序分析。结果:该CFEOM综合征家系为三代遗传,患病者8名,临床表型典型(1型)。基因直接测序及验证位点结果提示该家系的患者DNA中神经驱动蛋白家族(KIF)21A基因外显子20上存在一个杂合突变位点(c.2840T>C;p.M947T)与发病相关;该突变均出现于患者基因中,而未患病者无,证实其与疾病共分离。结论:成功定位一个CFEOM 1型家系的致病基因为KIF21A基因外显子20上的一个杂合突变。

Objective：To describe the clinical phenotype and causative genes in a Chinese family with autosomal domi nant congenital fibrosis of extraocular muscle（CFEOM）.Methods：A pedigree of congenital fibrosis of extraocular muscle was recruited.After informed consent was collected,a comprehensive clinic examination was performed,peripheral venous blood was taken from the family members,and genomic DNA was extracted.Coding exons of the KIF21 A gene were amplified using polymerase chain reaction analysis and sequenced directly for the family members.The detected muta tions were further analyzed in all available family members.Results：The subjects of this study were a pedigree of cong enital fibrosis of extraocular muscle（CFEOM 1）.The pedigree consisted of three generations of nineteen members inc luding eight patients.A heterozygous mutation,c.2840T〉C（p.M947T）,in KIF21A（kinesin family member 21A） was identified in the members with the disease in this family.The mutation was completely co-segregated with the disease phenotype in the family.Conclusions：The disorder in this family should be referred as CFEOM 1 and the causative gene of this pedigree is KIF21A.