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一型先天性眼外肌纤维化(Congenitalfibrosisoftheextraocularmuscles,CFEOM)是一种罕见的常染色体显性遗传的眼肌疾病,临床上主要表现为动眼神经缺陷而引起的斜视。本研究鉴定了具有四代病人的一个呈常染色体显性遗传的CFEOM1家系,连锁分析表明致病基因与染色体12q处的微卫星标记D12S85紧密连锁,最大LOD值为2.1。对D12S85附近的CFEOM1基因KIF21A进行突变检测,在KIF21A基因第21个外显子发现有一C→T的碱基替换,该变化引起KIF21A基因的第954位密码子由精氨酸突变为色氨酸,SSCP结果表明该家系中的所有患者都具有这一突变,而在家系中的所有正常人以及150个正常汉人对照中则不能检测到这一改变。我们的研究表明,KIF21A的p.Arg954Trp突变是引起这一先天性眼外肌纤维化家系病人患病的致病原因。
Congenital fibrosis (Congenital fibrosis of the extraocular muscle fibers, CFEOM) is a rare autosomal dominant ophthalmopathy, clinically manifested as eye defects caused by strabismus. In this study, an autosomal dominant CFEOM1 pedigree with four generations of patients was identified. Linkage analysis showed that the causative gene was closely linked to the microsatellite marker D12S85 at chromosome 12q with a maximum LOD value of 2.1. Mutation detection of KIF21A, a CFEOM1 gene near D12S85, revealed a C → T base substitution at exon 21 of KIF21A gene that resulted in the mutation of arginine to tryptophan at codon 954 of the KIF21A gene The SSCP results showed that all patients in this pedigree had this mutation, whereas this change was not detectable in all normal people in the pedigree as well as in 150 normal Han controls. Our study shows that p.Arg954Trp mutation in KIF21A is the causative agent responsible for the prevalence of this congenital extraocular muscle fibrosis pedigree patient.