家族性玻璃体淀粉样变性一家系的临床特征及基因分析

Clinical characteristics and gene analysis of vitreous amyioidosis in a Chinese kindreds

背景家族性玻璃体淀粉样变性是一种罕见的眼部局限性淀粉样变性疾病，属于常染色体显性遗传性疾病，可同时累及多个器官或组织；主要由甲状腺激素结合蛋白（TTR）基因突变导致。迄今为止，已报道100多种r豫基因突变，大多数分布在瑞士、葡萄牙、日本等国家，中国关于该病的突变家系报道较少。目的探讨家族性玻璃体淀粉样变性一家系的临床特征及基因突变特点。方法对一家系7代131人中的52人进行全身检查和眼部检查，对其外周血进行DNA抽提、PCR扩增、克隆、筛选及测序等检测TTR基因。其中8例13眼先后行经睫状体扁平部标准三通道玻璃体切割术，术后对病变玻璃体进行病理学检查。结果该家系成员52人中有17例发病，全身检查均未发现伴有神经系统、心脏、肾脏、肝脏等疾病；眼部检查显示，17例34跟有玻璃体混浊，15例28眼眼底有视网膜血管病变，10例16眼有白内障，无一例伴有青光跟、眼球运动障碍等眼部疾病。病理学检查显示，玻璃体刚果红染色呈阳性。基因检测发现，17例发病者及8人尚未发病者均发生了TTR基因第3外显子第83位氨基酸点突变Gly83Arg。结论，豫基因Arg一83突变所致玻璃体淀粉样变性家系临床特征为：不伴全身系统性疾病表现；跟底视网膜血管病变发病率高；不伴有青光服等其他眼部病变。

Background Familial vitreous amyloidosis is a rare ocular regional amyloidosis,and it is a kind of autosomal dominant inheritance disease. Familial vitreous amyloidosis demonstrates a variable penetrance due to the mutation in the plasma thyroid hormone-binding protein transtheretin （TTR） gene. Many studies have reported over 100 types of TTR genetic mutation in Switzerland,Portugal and Japan,but rare in China. Objective This survey aimed to investigate the clinical and genetic mutation characteristics in familial vitreous amy]oidosis. Methods Physical and eye examinations were performed on 52 family members of this vitreous amyloidosis family. Peripheral blood samples from 52 members were collected for TTR gene test by DNA extract, PCR amplification,clone,bolting and sequencing. Pars plana vitrectomy was firstly performed prior to the pathological examination of vitreous sample on 13 eyes of 8 members. Informed consent was obtained from each individual before any medical procedure. Results Seventeen members suffered from vitreous amyloidosis in this family without nervous system, heart, kidney and liver disease. Vitreous opacity was found in 34 eyes of the 17 members,and retinal vasculopathy was seen in 28 eyes of 15 members. In addition, cataract appeared in 16 eyes of 10 members. None of the members had glaucoma or ocular motility disorders. Congo red test of vitreous specimens showed a positive result in 13 eyes of 8 patients who received vitrectomy. Point mutation was verified on the 83th amine acid location of exon 3 （Gly83Arg） in TTR gene by gene sequencing. Conclusions Clinical characteristics of familial vitreous amyloidosis induced by TTR gene Arg-83 mutation is rate retinal vasculopathy without glaucoma, other ocular regional disease and systemic diseases.