两个汉族家族性玻璃体淀粉样变性家系突变基因检测及临床表型分析  

Genetic testing and clinical phenotypic analysis of familial vitreous amyloidosis in two Han Chinese families

作　　者：郑巍 李海波[1] 张雪咏 周学智 陈媛媛 毛俊峰[1] Zheng Wei;Li Haibo;Zhang Xueyong;Zhou Xuezhi;Chen Yuanyuan;Mao Junfeng(Department of Ophthalmology,Xiangya Hospital of Central South University,Changsha 410008,China)

机构地区：[1]中南大学湘雅医院眼科,长沙410008

出　　处：《中华实验眼科杂志》2021年第8期714-718,共5页Chinese Journal Of Experimental Ophthalmology

基　　金：湖南省卫计委项目(B20180915);长沙市自然科学基金项目(kq2014292)。

摘　　要：目的探讨2个汉族家族性玻璃体淀粉样变性(FVA)家系的临床特征及其基因突变特点。方法采用家系调查研究,收集2015年1月至2018年12月于中南大学湘雅医院就诊的2个汉族淀粉样变性家系,对家系成员进行全身及眼科检查,抽取外周静脉血,进行DNA抽提、PCR扩增、筛选及测序等检测转甲状腺素蛋白(TTR)基因。分别对2个家系的先证者行经睫状体平坦部标准三通道23G玻璃体切割术,术后对玻璃体样本行组织病理学检查。结果家系1的63名成员中有15例出现双眼玻璃体混浊,平均发病年龄为(43.6±5.8)岁;全身检查未发现神经系统、心血管系统、肾脏、肝脏病变;先证者术中玻璃体黏稠,难以切净;玻璃体标本刚果红染色呈阳性;术后伴发开角型青光眼,基因检测发现TTR基因第3外显子Gly83Arg突变。家系2的49名成员中有7例出现双眼玻璃体混浊,平均发病年龄为(50.4±5.5)岁;其中3例患者出现四肢麻木、肌力下降症状。先证者术中见玻璃体松软易于切割,玻璃体标本刚果红染色呈阳性反应,基因检测发现TTR基因第2外显子Ala36Pro突变,未伴发青光眼。结论TTR基因Gly83Arg或Ala36Pro突变可导致FVA,2个家系致病基因位点不同,其发病年龄、临床症状、并发其他系统疾病等临床表型也有所不同。Objective To investigate the clinical characteristics of two Han families with familial vitreous amyloidosis(FVA)and the gene mutation.Methods A pedigree investigation was performed.Two Han Chinese families with FVA treated in Xiangya Hospital of Central South University from January 2015 to December 2018 were collected.General examination and ophthalmic examination were performed among 112 members of the two families.Peripheral blood samples were collected from 32 family members(15 patients in MZ001 pedigree,7 patients in MZ002 pedigree,and 5 persons with normal clinical phenotype from each pedigree)for DNA extraction,polymerase chain reaction(PCR)amplification,transthyretin(TTR)gene screening and sequencing.Vitreous biopsy following three-channel 23-gauge pars plana vitrectomy was performed on the two probands in the two families.Vitreous specimens were sent for pathological examination.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Xiangya Hospital of Central South University(No.201412463),and written informed consent was obtained from all subjects before any medical examination.Results In MZ001,there were 15 cases of the 63 members presented bilateral vitreous opacity at an average age of(43.6±5.8)years.No lesion was found in nervous system,cardiovascular system,kidney or liver in general inspection.The vitreous of the proband(Ⅲ13)was so sticky that could not be totally removed during vitrectomy.The vitreous specimen showed positive Congo red staining.Ⅲ13 had elevated intraocular pressure after vitrectomy and was diagnosed as open-angle glaucoma.Gene sequencing revealed Gly83Arg mutation in the exon 3 of TTR gene.In MZ002,7 cases of 49 members had bilateral vitreous opacity at an average age of(50.4±5.5)years,among which,3 cases appeared symptoms of limb numbness and decreased muscle strength.The vitreous body of the proband(Ⅱ11)in MZ002 pedigree was looser and easier to remove during vitrectomy than that ofⅢ13 in MZ001 pedigree.Vitreous s

关 键 词：玻璃体淀粉样变性 临床表型 转甲状腺素蛋白 基因突变 汉族 家系分析 

分 类 号：R776.4[医药卫生—眼科]