中文摘要：

一型先天性眼外肌纤维化（Congenital fibrosis of the extraocular muscles, 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K1F21A进行突变检测，在K1F21A基因第21个外显子发现有一C→T的碱基替换，该变化引起K1F21A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，K1F21A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。

英文摘要：

Congenital fibrosis of the extraocular muscles type 1 （CFEOM1） is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. In this study, we identified a Chinese family with CFEOM1 for four generations. Linkage analysis mapped the causative gene of the family to 12q with a Lod score 2.1 for polymorphic marker D12S85, where KIF21A is located. Direct DNA sequence analysis identified a 2860C→T change in exon 21, resulting in a tryptophan substitution for arginine in codon 954 of KIF21A. SSCP （single-stranded conformational polymorphism） analysis showed that mutation p.Arg954Trp of KIF21A co-segregated with the affected members, but was absent in the unaffected individuals in the family and 150 normal controls. Our resuits indicate that mutation p.Arg954Trp of the KIF21A is the genetic basis of the Chinese family with CFEOM1.