Stargardt病一家系致病基因突变位点的研究与分析

The study and analysis of mutation sites of pathogenic genes in a family of Stargardt's disease

目的筛查并分析Stargardt病(STGD)家系的致病基因突变位点。方法采集6名Stargardt病家庭成员临床资料。行荧光素眼底血管造影(FFA)和频域相干光层析成像术(SD-OCT)、视网膜电图(ERG)、色觉、视野测试等。6名家庭成员抽外周血血送北京康旭医学检验所行基因检测。结果检测出致病基因突变8处,ABCA4基因c.1760+2T>G,USH2A基因c.7068T>G和c.9340C>T,FZD4基因c.205C>T,IMPDH1基因c.1405+9A>G,PRIMPOL基因c.265T>G,RB1基因c.2212-9C>A,TSC2基因c.856A>G。母亲含有3个突变,姐姐病情较弟弟轻,8个突变中含有4个,病情重的弟弟含有8个突变,姐弟两人前3个基因突变遗传均源于母亲。患者1双眼矫正视力0.3,患者2双眼矫正视力0.3.随访半年,患者1视力基本稳定在矫正视力0.3,患者2矫正视力较之前稍差,矫正0.2。结论本研究中,发现8个突变,其中3个来自于母亲的突变基因。ABCA4基因c.1760+2T>G,是明确的STGD致病基因,这个基因位于染色体1p22位置。USH2A基因c.7068T>G和c.9340C>Tc,致病性也曾被报道。姐姐含有RB1基因突变c.2212-9C>A。母亲未发病。造成姐姐和弟弟发病的原因可能是合并其他突变。同时作用造成临床表现严重,且临床发病时间不同。本研究发现的基因突变为Stargardt病的分子生物学研究进一步提供了参考依据,为临床患者遗传咨询、产前诊断等提供了信息。

Objective Screening and analyzing pathogenic gene mutation sites in Stargardt's disease pedigrees.Method Clinical data of 6 family members with Stargardt's disease were collected.Fundus fluorescein angiography,spectral domain-optical coherence tomography,electroretinogram,color blindness,visual field tests were performed.The peripheral blood of 6 family members was sent to Beijing Kangxu Medical Laboratory for genetic testing.Results Eight pathogenic gene mutations were detected.Respectively:ABCA4 gene,c.1760+2 T>G,USH2A gene,c.7068 T>G and c.9340C>T,FZD4 gene,c.205C>T,IMPDH1 gene,c.1405+9 A>G,PRIMPOL gene,c.265 T>G,RB1 gene,c.2212-9C>A,TSC2 gene,c.856 A>G.The mother had three mutations,the older sister had four of the eight mutations,and the more severe brother had eight.The first three gene mutations of both siblings were inherited from their mother.The corrected visual acuity of patient 1 was 0.3,and the corrected visual acuity of patient 2 was 0.3.Following up for half a year,the visual acuity of Patient 1 was basically stable at the corrected visual acuity of 0.3,while the corrected visual acuity of Patient 2 was slightly worse than before,corrected visual acuity of 0.2.Conclusions In this study,eight mutations were found,three of which were from the mother's mutated gene.ABCA4 gene c.1760+2T>G is a clear pathogenic gene of STGD,which is located at chromosome 1p22.The pathogenicity of the USH2A genes c.7068T>G and c.9340C>T has also been reported.All three mutations come from the mother.The elder sister contained RB1 gene mutation c.2212-9C>A.The mother did not become ill.The cause of the older sister and younger brother may be the combination of other mutations.The mutated gene simultaneously causes severe clinical manifestations and different clinical onset time.The gene mutations found in this study provide a reference for further molecular biological research of Stargardt's disease,and provide information for genetic counseling and prenatal diagnosis of clinical patients.