Molecular genetic analysis for inherited retinal degeneration and epidemiology

众所周知，进行性遗传性视网膜变性长期以来一直是一种难以治疗的疾病，因为它是一种遗传性和进行性疾病，迄今为止还没有有效的治疗方法。在本研究中，我们确定了日本Leber先天性黑蒙（LCA）患者7个基因（RPE 65、CRX、LRAT、GUCY 2D、CRB 1、AIPL 1和RDH 12）突变的类型和患病率，并将基因型与表型相关联。对72例无血缘关系的LCA患者的7个基因的所有外显子的编码序列及其相邻侧翼内含子序列进行了直接测序。通过视力、裂隙灯生物显微镜、视网膜电图、荧光素血管造影和动态视野检查来表征临床特征。在72例LCA患者中，3例（4%）发现6种致病突变。的 关于我们 RPE 65基因中的复合杂合子Arg 515 Trp和Arg 124 X、AIPL 1基因中的Leu 154 Pro和733- 735 delGAG突变以及RDH 12基因中的Lys 192 X和Gln 161 Trp突变与日本LCA患者的表型共分离。在3例不相关的LCA患者中发现RPE 65基因的杂合子Arg 515 Trp突变，然而，全基因测序未发现第二个突变等位基因。7个基因的致病突变发生率依次为：RPE 65 1.4%、CRX 0%、LRAT 0%、GUCY 2D 0%、CRBI 0%、AIPL 1 1.4%、RDH 12 1.4%。其中AIPL 1基因的Leu 154 Pro和733- 735 de 1GAG突变以及RDH 12基因的Lys 192 X和Gln 161 Trp突变为新突变。虽然遗传性视网膜变性表现出遗传异质性，但X连锁青少年视网膜劈裂症、眼底白斑症和无脉络膜症患者分别在RS 1、RDH 5和CHM基因中存在突变。这些结果表明，遗传分析在某些视网膜变性的诊断中起着重要作用。目的：探讨视网膜色素变性（RP）患者的心理状态及其与视功能的关系，并采用情绪状态量表（POMS）对RP患者的心理状态进行评估。本研究纳入了67例RP患者。本研究提示，尽管患者视功能较差，但眼科医生的长期观察可能使患者接受疾病，并使患者精神状态恢复正常。视网膜色素变性的病程是影响视网膜色素变性患者心理状态的最重要因素，而眼科检查结果则不是影响因素。少

It is well known that progressive inherited retinal degenerations have been a difficult disease to treat for a long time because it is an inherited and progressive disease, and an effective treatment is not available so far. For a long time, inherited retinal diseases were considered to result from a mutation of a gene, which plays an important role in the retina.In our present study, we determined the type and prevalence of mutations in 7 genes (RPE65, CRX, LRAT, GUCY2D, CRB1, AIPL1 and RDH12), in Japanese patients with Leber's congenital amaurosis (LCA), and to correlate the genotype to the phenotype. The coding sequence and the adjacent flanking intron sequences of all exons of the 7 genes were directly sequenced in 72 unrelated patients with LCA. The clinical features were characterized by visual acuity, slit-lamp biomicroscopy, electroretinography, fluorescein angiography, and kinetic visual field testing. 6 causative mutations were found in 3 of the 72 patients with LCA (4%). The … More compound heterozygous Arg515Trp and Arg124X in the RPE65 gene, the Leu154Pro and 733-735delGAG mutations in the AIPL1 gene, and the Lys192X and Gln161Trp mutations in the RDH12 gene cosegregated with the phenotype in Japanese patients with LCA. The heterozygous Arg515Trp mutation in the RPE65 gene was found in three unrelated patients with LCA, however, sequencing of the entire gene did not reveal a 2nd mutant allele. The prevalence of the causative mutations in the 7 genes were : RPE65, 1.4%; CRX, 0%; LRAT, 0%; GUCY2D, 0%; CRBI, 0%; AIPL1,1.4%) and RDH12,1.4%. Among these mutations-the Leu154Pro and 733-735de1GAG mutations in the AIPL1 gene, and the Lys192X and Gln161Trp mutations in the RDH12 gene were novel mutations. Although inherited retinal degeneration showed genetic heterogeneity, patients with X-linked juvenile retinoschisis, fundus albipunctatus and choroideremia have mutations in the RS1, RDH5, and CHM genes respectively. These findings suggested that genetic analyses played an important role for diagnosis for some retinal degenerations. We investigate the mental state, and the correlation between the emotional distress and visual functions of patients with retinitis pigmentosa(RP).The mental state of patients with RP was evaluated using the Profiles of Mood States(POMS). 67 patients with RP were included in this study. Our study suggested that long term observations by ophthalmologist might made patients accept the disease, and lead to normal mental satae, in spite of their poor visual functions. The period of having retinitis pigmentosa was the most important factor of the mental state of patients with RP rather than the results of ophthalmologic examinations. Less