Molecular genetic analysis for inherited retinal degeneration and epidemiology

进行性遗传性视网膜变性是一种遗传性进行性疾病，长期以来一直是治疗的难点，目前尚无有效的治疗方法。长期以来，遗传性视网膜疾病被认为是由一种在视网膜中起重要作用的基因突变引起的。在我们目前的研究中，我们确定了7个基因（RPE65， CRX， LRAT, GUCY2D, CRB1， AIPL1和RDH12）在日本Leber's先天性黑内障（LCA）患者中的突变类型和流行程度，并将基因型与表型相关联。对72例无亲缘关系的LCA患者的7个基因的编码序列及所有外显子的相邻侧翼内含子序列进行直接测序。临床表现为视力、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测试。72例LCA患者中有3例（4%）发现6个致病突变。在日本LCA患者中，RPE65基因中的Arg515Trp和Arg124X， AIPL1基因中的Leu154Pro和733-735delGAG突变，RDH12基因中的Lys192X和Gln161Trp突变与表型共分离。在3例无亲缘关系的LCA患者中发现了RPE65基因的Arg515Trp杂合突变，但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分别为：RPE65, 1.4%；CRX, 0%;LRAT, 0%;GUCY2D, 0%;CRBI, 0%;AIPL1,1.4%)和RDH12,1.4%。其中AIPL1基因的Leu154Pro和733-735de1GAG突变，RDH12基因的Lys192X和Gln161Trp突变为新突变。尽管遗传性视网膜变性具有遗传异质性，但x连锁青少年视网膜裂、白斑眼底和脉络膜血症患者分别存在RS1、RDH5和CHM基因突变。这些发现表明遗传分析在视网膜变性的诊断中起着重要的作用。目的探讨色素性视网膜炎（RP）患者的精神状态及情绪困扰与视觉功能的关系。采用情绪状态量表（POMS）评价RP患者的精神状态。67例RP患者纳入本研究。我们的研究表明，尽管患者的视觉功能较差，但眼科医生的长期观察可能使患者接受疾病，并导致正常的精神状态。色素性视网膜炎的发病时间是影响RP患者精神状态的最重要因素，而非眼科检查结果。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