先天性特发性眼球震颤家系FRMD7基因突变分析

Mutations analysis of FRMD7 gene in idiopathic congenital nystagmus families

目的分析先天性特发性眼球震颤(ICN)家系FRMD7基因的致病基因突变。方法收集苏北人民医院眼科就诊的6个ICN家系,抽取全部受检者的外周静脉血,采集同期100名正常人静脉血作为正常对照,提取基因组DNA,PCR扩增FRMD7基因的全部编码区及外显子-内含子交界区剪切位点附近的序列,Sanger测序法检测ICN家系潜在的致病突变。结果通过家系内基因型与表型的共分离验证,在其中2个家系中筛选出FRMD7基因3个致病突变:c.902A>G、c.1944T>A和c.1945G>T,其中错义突变c.1944T>A和无义突变c.1945G>T为新发现突变位点。在100个正常对照中未发现相同的突变。其余4个家系先证者FRMD7基因编码区及邻近剪切位点未发现相关有意义的突变。结论发现了FRMD7基因2个新的致病突变位点,扩展了ICN致病基因FRMD7的突变谱。

Objective To reveal the pathogenic mutations in Chinese families with idiopathic congenital nystagmus(ICN)Methods Six families with ICN were recruited from Subei People's Hospital.DNA was extracted from peripheral blood samples of all participants.All coding and exon-intronic boundary regions of the targeted gene FRMD7 were amplified with PCR and sequenced using Sanger sequencing to detect potential pathogenic mutations.This study followed the Helsinki Declaration and was approved by the Ethics Committee of Subei People's Hospital(NO.2015KY-126).All patients or their guardians signed informed consent.Results Three mutations(c.902A>G,c.1944T>A and 1945G>T)were screened in two families after co-segregation validation of intrafamilial genotype-phenotype,c.1944T>A and 1945G>T were newly detected mutations which were not detected in 100 normal controls.No significant mutations were found in the FRMD7 coding region and adjacent splicing sites in the probands of the other four families.Conclusions Two novel pathogenic mutations of FRMD7 are discovered,which expands the pathogenic mutational spectrum of FRMD7 gene causing ICN.