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，到目前为止还没有有效的治疗方法。长期以来，遗传性视网膜疾病被认为是视网膜中起重要作用的基因突变的结果。在本研究中，我们检测了7个基因(RPE65、CRX、LRAT、GUCY2D、CRB1、AIPL1和RDH12)在日本Leber先天性黑色素瘤(LCA)患者中的突变类型和发生率，并将其与表型进行了关联。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和相邻内含子序列进行了直接测序。临床表现包括视力、裂隙灯生物显微镜、视网膜电描记术、荧光素血管造影术和动态视野检查。72例LCA患者中有3例发现6个致病突变(4%)。The…RPE65基因Arg515Trp和Arg124X复合杂合子，AIPL1基因Leu154Pro和733-735delGAG突变，RDH12基因Lys192X和Gln161Trp突变与日本LCA患者的表型相关。在3例无血缘关系的LCA患者中发现RPE65基因Arg515Trp杂合性突变，但全基因测序未发现第二个突变等位基因。7个基因突变的发生率分别为：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突变以及RDH12基因的Lys192X和Gln161Trp突变是新的突变。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，遗传分析在某些视网膜退行性变的诊断中发挥了重要作用。为了解视网膜色素变性(RP)患者的心理状态及其与视功能的关系，采用情绪状态量表(POMS)对RP患者的心理状态进行评估。67例RP患者纳入本研究。我们的研究表明，眼科医生的长期观察可能会使患者接受这种疾病，并导致正常的心理状态，尽管他们的视觉功能很差。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，而不是眼科检查结果。较少

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