一个常染色体显性遗传先天性眼外肌 纤维化家系A

为寻找疾病相关基因,通过随访调查、体检、病理检查等手段,发现了一眼外肌纤维化家系4代中有15人患有眼外肌纤维化综合征,主要表现先天性上眼睑下垂、下颌上举、头后仰、双眼固定下转位和被动牵拉试验阳性,眼外肌病理检查结果为肌纤维化和玻璃样变性,所有阳性体征者除眼球运动限制程度有区别外,其他眼部症状基本相同。遗传分析表明,该疾病属常染色体显性遗传。该家系可作为寻找眼外肌纤维化疾病相关基因的宝贵资源。Abstract: To discover novel disease genes, a family with congenital fibrosis of the extraocular muscle was studied by a follow-up investigation, eye examinations and histo-pathological examination. There were fifteen cases suffering from congenital general fibrosis syndrome in four generations. They have congenital blepharoptosis, head tilt, chin lift, primary gaze fixed in a hypo- and exotropic position. The diagnosis is confirmed with positive forced duction testing in the affected eye. Furthermore, fibrosis of the extraocular muscles and hyaline degeneration was confirmed by histo-pathological examination. Except for different levels of restriction of the eyeball movements , other eye symptoms in positive patients are substantially identical. The genetic analysis showed that this disease was caused by autosomal dominant inheritance. The pedigree may be precious resource candidate for discovering disease gene related with congenital fibrosis of the extraocular muscle.     

KIF21A基因的p.Arg954Trp突变引起中国人先天性眼外肌纤维化

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。