散发型视网膜色素变性致病基因及其遗传方式观察

摘要

目的 观察宁夏地区散发型视网膜色素变性(RP)的致病基因及其遗传方式.方法 临床检查确诊为散发型RP(sRP)的患者49例以及家庭成员128名纳入研究.详细收集患者病史、家族史;患者以及家庭成员均行最佳矫正视力、裂隙灯显微镜、间接检眼镜、眼底彩色照相、视野、光相干断层扫描、全视野视网膜电图检查;采集患者及其家庭成员外周静脉血,提取全基因组DNA.采用外显子捕获技术对目前已知的230个视网膜疾病致病基因进行相关基因排查,确定候选致病基因突变位点;第二代测序技术直接测序法进行验证,并在家庭成员中进行共分离,分析其遗传方式.结果 49例sRP患者中,24例患者检测出致病基因16个,检测阳性率为49.0％;发现突变位点41个.其中,新发现突变位点32个,占78.0％.24例检测出致病基因的患者中,致病基因USH2A 7例,占29.2％;C20rf71、RDH12、CNGA1各2例,分别占8.3％;RPGR1、IFT140、TULP1、CLRN1、RPE65、ABCA4、GUCA1A、EYS、CYP4V2、GPR98、ATXN7各1例,分别占4.2％.根据其家庭成员基因筛查结果分析,24例检测出致病基因的患者中,隐性遗传RP20例,占83.3％;显性遗传RP 3例,占12.5％;X连锁遗传RP 1例,占4.2％.USH2A基因突变的7例患者中3例确诊为Usher综合征.结论 宁厦地区sRP患者主要致病基因为USH2A基因;检测出致病基因的患者中83.3％为常染色体隐性遗传RP.%Objective To observe the disease-causing genes and the inheritance in sporadic retinitis pigmentosa (sRP) in Ningxia region.Methods 49 sRP patients and 128 family members were recruited for this study.All the patients and family members received complete ophthalmic examinations including best corrected visual acuity,slit-lamp microscope,indirect ophthalmoscopy,fundus color photography,visual field,optic coherence tomography,full view electroretinogram.DNA was extracted from patients and family members.Using exon combined target region capture sequencing chip to screen the 230 candidate diseasecausing gene mutations,polymerase chain reaction and direct sequencing were used to confirm the diseasecausing mutations.Results 24/49 patients (49.0％) had identified disease-causing genes,totally 16 genes were involved.There were 41 mutation sites were found,including 32 new mutations (78.0％).The disease-causing genes include USH2A,C2orf71,GNGA1,RPGR1,IFT140,TULP1,CLRN1,RPE65,ABCA4,GUCA1,EYS,CYP4V2,GPR98 and ATXN7.Based on pedigree analysis,20 patients were autosomal recessive retinitis pigmentosa,3 patients were autosomal dominant retinitis pigmentosa and 1 patient was X linked retinitis pigmentosa.3/7 patients with USH2A mutations were identified as Usher syndrome.Conclusions USHZA is the main disease-causing of sRP patients in Ningxia region.83.3％ of sRP in this cohort are autosomal recessive retinitis pigmentosa.