CAJ | 학술논문

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.
일형선천성안외기섬유화(Congenital fibrosis of the extraocular muscles,CFEOM)시일충한견적상염색체현성유전적안기질병,림상상주요표현위동안신경결함이인기적사시.본연구감정료구유사대병인적일개정상염색체현성유전적CFEOM1가계,련쇄분석표명치병기인여염색체12q처적미위성표기D12S85긴밀련쇄,최대LOD치위2.1.대D12S85부근적CFEOM1기인KIF21A진행돌변검측,재KIF21A기인제21개외현자발현유일C→T적감기체환,해변화인기KIF21A기인적제954위밀마자유정안산돌변위색안산,SSCP결과표명해가계중적소유환자도구유저일돌변,이재가계중적소유정상인이급150개정상한인대조중칙불능검측도저일개변.아문적연구표명,KIF21A적p.Arg954Trp돌변시인기저일선천성안외기섬유화가계병인환병적치병원인.
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 results indicate that mutation p.Arg954Trp of the KIF21A is the genetic basis of the Chinese family with CFEOM1.