一个眼牙指发育不良家系的基因突变分析

Gene Mutation Analysis of an Oculodentodigital Dysplasia Pedigree

目的 旨在报道一个罕见的中国汉族眼牙指发育不良家系,并对该家系进行基因突变分析.方法 采用PCR及测序方法检测该家系先证者GJA1基因编码区及其侧翼序列的突变,然后在家系成员中验证,并通过Weblogo软件对可疑变异位点进行保守性分析;同时利用PCR、电泳及测序分析方法,检测HOXD13基因突变,排除患者由HOXD13基因突变致病的可能.结果 该家系内患者均携带GJA1基因的杂合突变c.605 C〉T,正常个体均无此突变;该突变导致Cx43蛋白第202位氨基酸由精氨酸变成组氨酸（p.R202H）;HOXD13基因未见异常.结论GJA1基因c.605 C〉T（p.R202H）突变是该中国汉族眼牙指发育不良家系的致病突变,该突变为中国人群中首次报道.

Objective Presented in this report was a rare pedigree of oculodentodigital dysplasia and the pedigree was analyzed to find causative gene mutation.Methods PCR and sequencing were performed to detect mutations in GJA1 gene-coding region and its flanking sequences,and then validation was carried in family members.Weblogo software was used for analyzing conservation of suspicious mutation site.By using PCR,electrophoresis and sequencing,we examined HOXD13 gene mutations to exclude the possibility of HOXD13 mutation as a cause of the disease.Results All the patients in the family carried a c.605C〉T heterozygous mutation of GJA1 gene,while the normal individuals had no mutations in GJA1.This mutation leads to substitution of 202th arginine to histidine in Cx43 protein.No mutations were found in HOXD13 gene.Conclusion c.605C〉T （p.R202H）mutation in GJA1 gene is the causative mutation of this Chinese oculodentodigital dysplasia pedigree,and the mutation was first reported in Chinese.