视网膜色素变性分子遗传学研究现状

视网膜色素变性是由于视网膜感光细胞和色素上皮细胞变性导致夜盲和进行性视野缺损的最常见的遗传性眼底病 ,具有大的临床和遗传异质性。其遗传方式可为常染色体显性、常染色体隐性、X染色体连锁遗传和散发型。目前已发现RP相关基因 1 4种 ,其中常染色体显性遗传 4种 ,常染色体隐性遗传 8种 (包括视紫质 ) ,X染色体连锁遗传 2种。本文着重阐述了已知RP相关基因的研究现状。     

视网膜色素变性分子遗传学研究现状

视网膜色素变性是由于视网膜感光细胞和色素上皮细胞变性导致夜盲和进行性视野缺损的最常见的遗传性眼底病，具有大的临床和遗传异质性。其遗传方式可为常染色体显性、常染色体隐性、Ｘ染色体连锁遗传和散发型。目前已发现ＲＰ相关基因１４种，其中常染色体显性遗传４种，常染色体隐性遗传８种（包括视紫质），Ｘ染色体连锁遗传２种，本文着重阐述了已知ＲＰ相关基因的研究现状。     

信息快递

视网膜色素变性 (ＲＰ)在临床上尚无有效的治疗方法 ,随着分子生物学的发展 ,基因治疗是解决该病的最终道路 ,本期将介绍ＲＰ基因治疗的新进展。视网膜组织因子治疗最常见的途径有玻璃体腔内注射和视网膜下腔注射 ,尽管视网膜下注射可导致局限性的视网膜脱离 ,但仍是最有效的接近感光细胞的方法。1　常染色体隐性遗传变性　这种类型的疾病是由于基因突变 ,基因产物的缺乏引起的 ,对于这种类型 ,把正常基因导入感光细胞内 ,产生正常的基因表现型 ,稳定表达即可。在多种视网膜色素变性的实验动物模型中 ,以腺病毒、腺相关病毒、单疱病毒、痘苗…     

视网膜色素变性与基因突变

视网膜色素变性 (RP)是常见的致盲性遗传疾病 ,目前已发现有数十个基因的 15 0多个突变位点与其有关。与常染色体显性遗传、常染色体隐性遗传和性连锁遗传相对应的最常见的突变基因分别是视红紫质基因、杆体环鸟苷酸磷酸二脂酶基因和三磷酸鸟苷酸酶调节因子基因 ,其他的突变基因还有盘膜边缘蛋白基因 (常染色体显性遗传 )、杆体环鸟苷酸离子通道基因、RPE6 5基因、视黄醛结合蛋白基因和酪氨酸激酶受体基因 (常染色体隐性遗传 ) ,RP2基因(性连锁遗传 ) ,线粒体DNA细胞色素b基因等 ,每个突变基因对应于人群中不同的RP患者。基因治疗将成为治疗RP的根本方法 ,而对RP突变基因的定位、基因的生物学功能、突变所造成的分子病理机制的深入认识 ,是进行基因治疗的关键。     

Y连锁遗传的视网膜色素变性(附一家系报告)

视网膜色素变性(Retinitis pigmenfosa)是眼科常见的单基因遗传病,其遗传方式一般认为常染色体隐性,常染色体显性及x连锁隐性遗传。1987年5月,我们发现视网膜色素变性一家系,四代人共26人,其中8例男性,均系患者,女性则无1例患此病,其后代也无遗传者,经家谱分析,符     

视网膜色素变性的相关基因研究进展

视网膜色素变性(RP)是由于视网膜感光细胞和色素上皮细胞变性导致夜盲和进行性视野缺损的一种常见的、遗传性、致盲性眼底病,具有较大的临床和遗传异质性。迄今通过连锁分析和侯选基因筛查,已有14个常染色体显性遗传ADRP;20个常染色体隐性遗传ARRP和5个X-染色体连锁遗传型XLRP位点被定位,其中32个基因已被克隆,每种遗传方式都有多个基因被克隆。对于这些致病基因的结构、突变及其功能目前已经有了新的研究进展。     

结晶样视网膜色素变性临床与基础研究的机遇与挑战

结晶样视网膜色素变性（Bietti crystalline dystrophy,BCD）是视网膜色素变性中的一种特殊类型,其在东亚人群特别是中国人和日本人中较为常见。BCD的遗传方式为常染色体隐性遗传,唯一的致病基因为CYP4V2。对BCD患者自然史和CYP4V2突变导致BCD机制研究,将对确定BCD患者基因治疗的时间窗、临床研究中治疗效果评定以及探索治疗BCD其他方法均至关重要。（眼科,2020,29： 84-86）     

基于RCS大鼠模型的视网膜色素变性治疗

视网膜色素变性是一类以光感受器细胞及色素上皮细胞功能丧失为共同表现的疾病,具有遗传倾向性,通过选择不同的视网膜色素变性(relinitis pigmentosa,RP)动物模型可以针对不同遗传方式的RP进行研究,皇家外科学院(royal college surgeons,RCS)大鼠是常染色体隐性遗传的经典动物模型,现将基于RCS大鼠模型的RP治疗研究进展综述如下.     

药物治疗与基因治疗视网膜色素变性研究进展

视网膜色素变性（RP）是一组遗传性退行性视网膜疾病，主要影响视杆细胞和视网膜色素上皮细胞（RPE）。早期特征性临床表现为夜盲和周边视野的丧失，最终导致中心视力的丧失。RP全世界发病率为1／3500，它具有多种遗传方式，其中常染色体显性遗传（ADRP）占15％～20％，常染色体隐性遗传（ARRP）占20％～25％，X染色体连锁遗传（XLRP）占10％～15％，散发型占40％～45％。近来在药物治疗及基因治疗RP方面取得了一些进展，下面就对这两方面进行综述。     

视网膜色素变性治疗的研究进展

视网膜色素变性(retinitis pigmentosa,RP)是由视网膜光感受器和视网膜色素上皮变性所引起的致盲性、遗传性眼病,目前尚无有效的治疗方法,相关治疗研究还处于探索阶段,如基因治疗、药物治疗、移植治疗、人工视网膜假体等。基因治疗RP是目前的研究热点,包括修复致病基因、核酸治疗、RNA干扰技术等。基因治疗、干细胞移植、人工视网膜假体治疗RP已经进入临床试验阶段,为治疗该病带来了新的希望。本文就RP治疗的研究进展做一综述。     

On variants and disease-causing mutations: Case studies of a SEMA4A variant identified in inherited blindness

The p.R713Q variant of the semaphorin‐4a‐encoding gene, SEMA4a, has been reported to cause autosomal dominant retinitis pigmentosa. Here we show three families with retinal degeneration in which unaffected family members are either homozygous or heterozygous for the variant. The p.R713Q variant in SEMA4A is insufficient to cause either autosomal recessive or autosomal dominant retinitis pigmentosa and is unlikely to be pathogenic.     

Genetic features of retinitis pigmentosa in Turkey

Sixty-two cases with retinitis pigmentosa from 42 index families were investigated to reveal the genetic features of the disease in Turkey. There were 42 propositi of whom 5 had a systemic syndrome associated with retinitis pigmentosa. Of the remaining 37 cases the condition was autosomal recessive in 21 (56.8%), sporadic in 12 (32.4%), autosomal dominant in 3 (8.1%) and X-linked recessive in one (2.7%). Sporadic cases may be more frequent as many hereditary cases are not brought to medical attention in rural families. Male preponderance among sporadic cases may indicate that there may be more X-linked cases. Nine out of 21 cases initially classified as sporadic displayed parental consanguinity and they were included as having autosomal recessive trait. Large families with autosomal recessive inheritance may prove valuable in linkage analysis and in defining future gene abnormalities.     

An epidemiogenetic study of typical retinitis pigmentosa in Japan--a preliminary report of nationwide, multicenter study]

We performed a nationwide, multicenter study of typical retinitis pigmentosa with reference to the inheritance patterns of the disease. A total of 253 probands were registered during two months of 1989, and an analysis of the parental consanguinity of 182 probands with the method of inbreeding coefficient enabled us to estimate the relative prevalence of genetic types; autosomal recessive trait: 47.6%; autosomal dominant trait: 17.3%; sporadic cases: 34.6%. A comparison of the results with previous studies has indicated a decrease in the prevalence of the autosomal recessive trait and an increase in the sporadic cases, as would be expected from the decrease in consanguineous marriages and offsprings in the past few decades in Japan. X-linked retinitis pigmentosa was rarely identified, but precise evaluation of its frequency needs further investigation.     

Electroretinographic testing as an aid in detection of carriers of X-chromosome-linked retinitis pigmentosa.

Twenty-two of 23 obligate female carriers in nine families with known X-chromosome-linked retinitis pigmentosa were detected on the basis of abnormal full-field electroretinograms (ERGs). Only 14 of these carriers had fundus findings characteristic of the carrier state. Electroretinograms of carriers were either reduced in amplitude to white light under dark-adapted conditions or delayed in cone b-wave implicit time, or both. Daughters of obligate carriers had either normal ERGs or abnormal ERGs similar to those recorded from obligate carriers. Abnormal ERGs of carriers of X-chromosome-linked retinitis pigmentosa contrasted with the normal ERGs recorded from female carriers of autosomal recessive disease. These data support the idea that ERG testing of female relatives of males with retinitis pigmentosa can help to establish for a given family whether the mode of inheritance is X-chromosome-linked or autosomal recessive.     

Correlation between Goldmann perimetry and maximal electroretinogram response in retinitis pigmentosa

To evaluate the relationship between Goldmann perimetry and maximal electroretinographic responses in patients with retinitis pigmentosa, analyses were performed on 220 affected subjects and separately on two subgroups with autosomal dominant (n = 35) and autosomal recessive (n = 29) inheritance. Electroretinograms were recorded averaging 100 iterations elicited with a 20-lux/s, 0.5-Hz white flash ganzfeld stimulation. The peripheral isopters of the visual fields were delimited with I4e, IIIe and V4e targets, measured on conventional perimetry charts with a light pen and expressed in square centimeters. Unlike most previously published reports, this investigation showed a definite correlation (p = 0.0001) between maximal electroretinographic response amplitude and visual field areas. This correlation was more evident for I4e and IIIe isopters (r = 0.89 and 0.87, respectively) than for V4e isopter (r = 0.69). This phenomenon appears to be related to distortion occurring on standard isometric charts and to spatial summation effects in the peripheral field. Such correlations held for both the autosomal dominant and autosomal recessive subgroups. It appears that, if enough accuracy is provided, maximal electroretinographic responses and Goldmann visual fields are both good measures of the remaining functioning retina in nonsyndromic retinitis pigmentosa, irrespective of inheritance models and dystrophic patterns.Abbreviations ADRP autosomal dominant retinitis pigmentosa - ARRP autosomal recessive retinitis pigmentosa - RP retinitis pigmentosa - VF visual field     

Normal interaction of plasma retinol-binding protein from retinitis pigmentosa with bovine pigment epithelium.

The interaction between retinol-binding protein and normal bovine pigment epithelium has been studied with the use of iodinated retinol-binding protein isolated from the plasma of patients with the recessive form of retinitis pigmentosa and of normal subjects. It is concluded that the capacity of the plasma carrier protein to interact with the retinol-binding protein receptor of bovine pigment epithelium is unimpaired in retinitis pigmentosa with autosomal recessive inheritance.     

A survey of hereditary aspects of pigmentary retinal dystrophies

A study of 707 cases of retinitis pigmentosa and choroideraemia presenting over 12 years were classified according to their modes of inheritance-439 autosomal recessive (62%), 193 autosomal dominant (27%), 75 X-linked (10.7%). The patients with autosomal recessive transmission included 58 Usher syndrome, 12 Laurence-Moon-Bardet-Biedl syndrome and 33 Leber's congenital amaurosis. Another 37 had an early onset with macular degeneration and 31 were of late onset with pericentral dystrophy. Forty two were offspring of consanguineous parents. Of 193 individuals (78 families) with autosomal dominant inheritance, 20% had night blindness from early childhood. With X-linked transmission, 33 males and 31 female carriers comprised the retinitis pigmentosa group and eight males and three carrier females, choroideraemia. Almost all this X-linked group were of British ancestry. Of patients originating from the Mediterranean area, 94% had autosomal recessive disease.     

常染色体隐性遗传视网膜色素变性的相关基因研究进展

视网膜色素变性(rentinitis pigmentosa，RP)是一种发病机制尚未完全明确的遗传性致盲性视网膜疾病，特征性表现为夜盲、进行性视野缩窄和视力下降，眼底可见骨细胞样色素沉着、视网膜血管变细和视盘蜡黄三联症。RP具有较大的遗传异质性和临床异质性，其中常染色体隐性遗传视网膜色素变性(autosomal recessive RP，ARRP)占RP的5%～20%，目前已定位43个致病基因，克隆了其中40个，并且不断有新的相关致病基因被报道。本文就近3a发现与ARRP相关的AGBL5、ARHGEF18、HGSNAT和ZNF408四个基因研究进展作一综述。     

A survey of hereditary aspects of pigmentary retinal dystrophies

A study of 707 cases of retinitis pigmentosa and choroideraemia presenting over 12 years were classified according to their modes of inheritance--439 autosomal recessive (62%), 193 autosomal dominant (27%), 75 X-linked (10.7%). The patients with autosomal recessive transmission included 58 Usher syndrome, 12 Laurence-Moon-Bardet-Biedl syndrome and 33 Leber's congenital amaurosis. Another 37 had an early onset with macular degeneration and 31 were of late onset with pericentral dystrophy. Forty two were offspring of consanguineous parents. Of 193 individuals (78 families) with autosomal dominant inheritance, 20% had night blindness from early childhood. With X-linked transmission, 33 males and 31 female carriers comprised the retinitis pigmentosa group and eight males and three carrier females, choroideraemia. Almost all this X-linked group were of British ancestry. Of patients originating from the Mediterranean area, 94% had autosomal recessive disease.     

Analysis of the DNA of patients with retinitis pigmentosa with a cellular retinaldehyde binding protein cDNA

We used a cDNA fragment corresponding to the human cellular retinaldehyde binding protein (CRALBP) gene to search for mutations at this locus in patients with autosomal dominant, autosomal recessive, or isolate retinitis pigmentosa, and Usher's syndrome, type I. No gene deletions or rearrangements could be detected in any patient by Southern blotting. We identified a Pvu II restriction fragment length polymorphism (RFLP) defining two alleles at the CRALBP locus in the normal population. We used this RFLP to analyze the genomic DNA of large sets of unrelated patients with autosomal dominant, autosomal recessive, or isolate retinitis pigmentosa. Within each of these groups, RFLP alleles at the CRALBP locus showed no linkage disequilibrium (departure from Hardy-Weinberg equilibrium). In addition, two autosomal dominant, two autosomal recessive, and three Usher's syndrome, type I pedigrees each showed no cosegregation of the CRALBP locus and the disease locus. We could find no evidence that mutations of the CRALBP gene are associated with the common forms of retinitis pigmentosa or Usher's syndrome, type I.