CAJ | 학술논문

目的研究X-连锁隐性遗传视网膜色素变性(RP)家系RPGR基因突变男性患者和女性携带者的临床表型.方法家系调查研究.收集RP先证者及其家系资料,完善眼科检查,抽取现存77名家系成员和80名正常对照者外周静脉血,提取DNA,进行聚合酶链反应(PCR),扩增RPGR基因外显子ORF15,扩增产物纯化后直接测序.结果 RP家系中,8例RP患者均为男性,呈隔代传递,不存在男性至男性的传递,患者的母亲及女儿都是致病基因携带者而不发病,符合X-连锁隐性遗传方式.在8例男性RP患者和14例女性致病基因携带者的RPGR基因外显子ORF15+577_578位点发现一个AG缺失突变,引起阅读框架的改变,该基因缺失突变在家系中共分离.AG缺失突变导致男性患者典型的RP改变,但发病时间和进展程度不一.携带有杂合型基因突变的14例女性携带者最具特征性的临床表型是中高度近视眼(-5.00～-22.00 D).结论该RP家系患者由RPGR 基因外显子ORF15移码突变致g.ORF15+577_578delAG位点缺失.RPGR基因外显子ORF15的新突变可导致男性患者严重的RP表型,但女性致病基因携带者仅表现为中高度近视眼.(中华眼科杂志,2011,47:516-520)
목적 연구X-련쇄은성유전시망막색소변성(RP)가계RPGR기인돌변남성환자화녀성휴대자적림상표형.방법 가계조사연구.수집RP선증자급기가계자료,완선안과검사,추취현존77명가계성원화80명정상대조자외주정맥혈,제취DNA,진행취합매련반응(PCR),확증RPGR기인외현자ORF15,확증산물순화후직접측서.결과 RP가계중,8례RP환자균위남성,정격대전체,불존재남성지남성적전체,환자적모친급녀인도시치병기인휴대자이불발병,부합X-련쇄은성유전방식.재8례남성RP환자화14례녀성치병기인휴대자적RPGR기인외현자ORF15+577_578위점발현일개AG결실돌변,인기열독광가적개변,해기인결실돌변재가계중공분리.AG결실돌변도치남성환자전형적RP개변,단발병시간화진전정도불일.휴대유잡합형기인돌변적14례녀성휴대자최구특정성적림상표형시중고도근시안(-5.00～-22.00 D).결론 해RP가계환자유RPGR 기인외현자ORF15이마돌변치g.ORF15+577_578delAG위점결실.RPGR기인외현자ORF15적신돌변가도치남성환자엄중적RP표형,단녀성치병기인휴대자부표현위중고도근시안.(중화안과잡지,2011,47:516-520)
Objective To screen the mutation in the RPGR gene in a large Chinese family with X-linked recessive retinitis pigmentosa (RP) and to describe the phenotype in affected males and female carriers. Methods Ophthalmic examinations were performed in 77 family members of a RP pedigree to identify affected individuals. Polymerase chain reaction (PCR) and direct sequencing were used for screening of mutations in RPGR gene exon ORF15. Results Mutation screening demonstrated a novel mutation, g.ORF15+577_ 578delAG, which caused an open reading frameshift and resulted in premature truncation of the RPGR protein. This mutation was detected in 8 affected male individuals and 14 obligate female carriers in this family and was found to segregate with the phenotype in this family. This mutation led to a severe RP phenotype in male affected individuals with some variability in the age of onset of night blindness and loss of visual acuity, but was recessive in female carriers without a RP phenotype. However the most striking phenotypic feature in female carriers in this pedigree was moderate to high myopia with refractive error ranging from -5.00 D to -22.00 D in 14 female carriers. Conclusions This novel mutation in RPGR ORF15 causes serious RP phenotype in males and no RP phenotype in female carriers. Moderate to high myopia was a particular feature for female carriers in this pedigree. Our finding expands the spectrum of RPGR mutations causing RP and phenotypic spectrum of the disease in Chinese family, which is useful for further genetic consultation and genetic diagnosis.