视网膜色素变性患者RP1基因点突变频率及其特征:101例分析
시망막색소변성환자RP1기인점돌변빈솔급기특정:101례분석
Frequency and characteristics of retinitis pigmentosa I gene point mutation in patients with retinitis pigmentosa: 101 case analysis
  • 万方数据
    中国临床康复 중국림상강복
    CHINESE JOURNAL OF CLINICAL REHABILITATION
    2005年 6期 244-246 ,共3页

    张晓莉%杨冠寅%彭智培%府伟灵

    장효리%양관인%팽지배%부위령

    视网膜炎,色素性/遗传学%基因%突变%电泳,聚丙烯酰胺凝胶%序列分析,DNA 視網膜炎,色素性/遺傳學%基因%突變%電泳,聚丙烯酰胺凝膠%序列分析,DNA
    시망막염,색소성/유전학%기인%돌변%전영,취병희선알응효%서렬분석,DNA
    背景:视网膜色素变性(retinitis pigmentosa,RP)是一组最常见的遗传性致盲眼底病,在遗传和表型上均具有较大的异质性.1999年Pierce等发现了一个新的视网膜感光细胞特异基因--RP1,之后的研究发现该基因的突变可导致常染色体显性遗传RP(autosomal dominant RP,adRP).目前RP1的分子遗传学研究还主要集中在白种人群.目的:研究RP1基因在中国RP患者中的突变频率、特征及其在Rp发病机制中所起的作用.设计:以RP患者为研究对象健康人为对照组的观察对比研究.单位:一所军医大学医院基因诊断治疗中心.对象:101例无亲缘关系的RP患者均系香港威尔士亲王医院眼科门诊及香港眼科医院1998-01/2001-12的就诊患者,年龄10～79岁(男43例,女58例),平均年龄40岁.纳入标准:符合国内外RP诊断的通用标准者(包括眼底镜观察及视网膜电图测试).排除标准:其他视网膜眼底病变患者.对照组为190例健康成年人(无RP家族史及眼部检查无RP及其它眼部疾患),以确定所检测到的变异是否系RP1基因的多态现象.方法:在101例RP患者中运用构象敏感凝胶电泳(conformation sensitive gel electrophoresis,CSGE)和DNA直接测序方法检测RP1基因全编码区范围内的点突变.主要观察指标:RP1基因在中国RP患者中的突变频率、类型及在RP发病机制中的作用.结果:本研究中RP1基因在所有RP患者中的突变检出率为1/101,突变最终导致RP1蛋白严重截短,疾病的表型可能源于功能性RP1蛋白合成量的不足.此外在本研究人群中还发现10个错义突变,除M479I的病理意义未确定之外,其余均系RP1基因的多态现象.结论:RP1蛋白中相应片段(密码子1052～1933)的缺失会导致RP的发生.大范围的RP1基因分型工作是有必要的,并且可同时发现更多的RP致病突变以及不同于其他种族人群的RP1基因多态变化,进而从根本上治疗RP,彻底提高其患者的生活质量.
    배경:시망막색소변성(retinitis pigmentosa,RP)시일조최상견적유전성치맹안저병,재유전화표형상균구유교대적이질성.1999년Pierce등발현료일개신적시망막감광세포특이기인--RP1,지후적연구발현해기인적돌변가도치상염색체현성유전RP(autosomal dominant RP,adRP).목전RP1적분자유전학연구환주요집중재백충인군.목적:연구RP1기인재중국RP환자중적돌변빈솔、특정급기재Rp발병궤제중소기적작용.설계:이RP환자위연구대상건강인위대조조적관찰대비연구.단위:일소군의대학의원기인진단치료중심.대상:101례무친연관계적RP환자균계향항위이사친왕의원안과문진급향항안과의원1998-01/2001-12적취진환자,년령10～79세(남43례,녀58례),평균년령40세.납입표준:부합국내외RP진단적통용표준자(포괄안저경관찰급시망막전도측시).배제표준:기타시망막안저병변환자.대조조위190례건강성년인(무RP가족사급안부검사무RP급기타안부질환),이학정소검측도적변이시부계RP1기인적다태현상.방법:재101례RP환자중운용구상민감응효전영(conformation sensitive gel electrophoresis,CSGE)화DNA직접측서방법검측RP1기인전편마구범위내적점돌변.주요관찰지표:RP1기인재중국RP환자중적돌변빈솔、류형급재RP발병궤제중적작용.결과:본연구중RP1기인재소유RP환자중적돌변검출솔위1/101,돌변최종도치RP1단백엄중절단,질병적표형가능원우공능성RP1단백합성량적불족.차외재본연구인군중환발현10개착의돌변,제M479I적병리의의미학정지외,기여균계RP1기인적다태현상.결론:RP1단백중상응편단(밀마자1052～1933)적결실회도치RP적발생.대범위적RP1기인분형공작시유필요적,병차가동시발현경다적RP치병돌변이급불동우기타충족인군적RP1기인다태변화,진이종근본상치료RP,철저제고기환자적생활질량.
    BACKGROUND: Retinitis pigmentosa(RP) is a group of commonest genetic blindness-inducing eyeground diseases, which have relative great heterogenicity in both heredity and phenotype. Pierce et al discovered a new retinal photoreceptor cell specific gene-RP1 in 1999, and also found in their following research that the mutation of this gene can induce autosomal dominant RP(adRP) . Present RP1 molecular genetic researches mainly concentrate in Caucasians.OBJECTIVE: To investigate the mutation frequency, characteristics of RP1gene in Chinese RP patients and its role in RP pathogenesis.DESIGN: A comparative study by employing RP patients as subjects and healthy individuals as control.SETTING: Gene diagnosis and therapy center in a hospital affiliated to a military medical university of Chinese PLA.PARTICIPANTS: Totally 101 RP patients without genetic classification were visited patients of the outpatient Department of Ophthalmology of Hong Kong Prince Wales Hospital and Hong Kong Hospital of Ophthalmology between January 1998 and December 2001, which aged between 10 and 79years old(including 43 male and 58 female cases) with an average age of 40years old. Inclusive criteria: Cases who were in accordance with the general national and international standards for RP diagnosis(including funduscope observation and electroretinogram test). Exclusive criteria: patients of other retinal pathological changes. A total of 190 healthy adults were selected in control group, which had no RP family history and no RP or other eye diseases in eye examination, for the confirmation of whether the detected variation was the polymorphism of RP1 gene.METHODS: Totally 101 cases received conformation sensitive electrophoresis(CSGE) and DNA direct sequencing analyses to detect the point mutation in entire RP1 gene encoding range.MAIN OUTCOME MEASURES: Mutation frequency and patterns of RP1gene in Chinese RP patients and its role in RP pathogenesis.RESULTS: The mutation detectable rate of RP1 gene in all PR patients was 1/101. Mutation ultimately caused serious truncation in RP1 protein. The phenotype of the disease might be originated from functional deficiency in PR1protein synthesis. In addition, 10 missense mutations were found in our study population, most of which were RP1 gene polymorphism except the unconfirmed pathological significance of M479I.CONCLUSION: The deletion of corresponding segments(codon 1052-1933) in RP1 protein would induce RP. Large-scale RP1 genotying is necessary, which also can discover more RP-inducing mutation and RP1 gene polymorphism different from other races simultaneously for further fundamental therapy of RP and thorough improvement of the quality of life of the patients.
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