CAJ | 학술논문

目的：探讨外显子结合目标区域捕获测序芯片检测视网膜色素变性（ RP）家系的致病基因的可行性。方法家系调查研究。选择2010年10月至2012年12月在宁夏眼科医院就诊的10个RP家系作为研究对象。收集所有患者及其家庭成员临床资料，完善眼科检查，抽取患者、家系成员及其正常对照者外周静脉血，提取DNA，运用外显子结合目标区域捕获测序芯片进行检测，对检测结果进行分析后得到候选致病性突变位点。运用PCR和直接测序进行验证，确定致病性突变位点。结果10个家系中共收集患者17例，健康家庭成员23名。10个家系中常染色显性遗传家系1个，其余9个为常染色隐性遗传。5个家系最终检测到7个突变位点，涉及5个基因。2号家系检测到BBS7基因的1个移码突变，该家系患者同时合并向心性肥胖、多指畸形和智力缺陷，最终确定为Bardet-Biedl综合征。7号和10号两个隐性遗传家系分别检测到1个USH2A基因的错义突变，患者同时合并耳聋，诊断为Usher综合征，其中7号家系还检测到年龄相关性黄斑变性（ AMD）相关基因C3的1个错义突变位点。1号家系在CRB1基因上检测到1个无义突变和1个错义突变，5号家系在PROM1基因上检测到1个剪切突变。结论外显子结合目标区域捕获测序芯片可以对RP进行快速、有效的基因诊断，结合临床特征分析有助于提高RP的临床诊断水平。（中华眼科杂志，2014，50：434-439）
목적：탐토외현자결합목표구역포획측서심편검측시망막색소변성（ RP）가계적치병기인적가행성。방법가계조사연구。선택2010년10월지2012년12월재저하안과의원취진적10개RP가계작위연구대상。수집소유환자급기가정성원림상자료，완선안과검사，추취환자、가계성원급기정상대조자외주정맥혈，제취DNA，운용외현자결합목표구역포획측서심편진행검측，대검측결과진행분석후득도후선치병성돌변위점。운용PCR화직접측서진행험증，학정치병성돌변위점。결과10개가계중공수집환자17례，건강가정성원23명。10개가계중상염색현성유전가계1개，기여9개위상염색은성유전。5개가계최종검측도7개돌변위점，섭급5개기인。2호가계검측도BBS7기인적1개이마돌변，해가계환자동시합병향심성비반、다지기형화지력결함，최종학정위Bardet-Biedl종합정。7호화10호량개은성유전가계분별검측도1개USH2A기인적착의돌변，환자동시합병이롱，진단위Usher종합정，기중7호가계환검측도년령상관성황반변성（ AMD）상관기인C3적1개착의돌변위점。1호가계재CRB1기인상검측도1개무의돌변화1개착의돌변，5호가계재PROM1기인상검측도1개전절돌변。결론외현자결합목표구역포획측서심편가이대RP진행쾌속、유효적기인진단，결합림상특정분석유조우제고RP적림상진단수평。（중화안과잡지，2014，50：434-439）
Objective To detect the disease-causing genes of 10 retinitis pigmentosa pedigrees by using exon combined target region capture sequencing chip.Methods Pedigree investigation study.From October 2010 to December 2013, 10 RP pedigrees were recruited for this study in Ningxia Eye Hospital.All the patients and family members received complete ophthalmic examinations.DNA was abstracted from patients,family members and controls.Using exon combined target region capture sequencing chip to screen the candidate disease-causing mutations.Polymerase chain reaction ( PCR) and direct sequencing were used to confirm the disease-causing mutations.Results Seventy patients and 23 normal family members were recruited from 10 pedigress.Among 10 RP pedigrees , 1 was autosomal dominant pedigress and 9 were autosomal recessive pedigrees.7 mutations related to 5 genes of 5 pedigrees were detected.A frameshift mutation on BBS7 gene was detected in No.2 pedigree,the patients of this pedigree combined with central obesity,polydactyly and mental handicap.No.2 pedigree was diagnosed as Bardet-Biedl syndrome finally.A missense mutation was detected in No .7 and No.10 pedigrees respectively.Because the patients suffered deafness meanwhile ,the final diagnosis was Usher syndrome.A missense mutation on C3 gene related to age-related macular degeneration was also detected in No.7 pedigress.A nonsense mutation and a missense mutation on CRB1 gene were detected in No.1 pedigree and a splicesite mutation on PROM1 gene was detected in No.5 pedigree.Conclusions Retinitis pigmentosa is a kind of genetic eye disease with diversity clinical phenotypes.Rapid and effective genetic diagnosis technology combined with clinical;characteristics analysis is helpful to improve the level of clinical diagnosis of RP.