Molecular Genetic Studies of Important Eye Diseases

这项研究涉及到重要眼病的分子遗传学分析。主要研究结果如下：1.研究结果。诺里病诺里病是一种罕见的X连锁疾病，在婴儿中表现为严重的玻璃体视网膜发育不良。我们之前在鹿儿岛县发现了两个家庭，在这次研究期间，在东京和千叶又发现了两个家庭。对这四个家系进行了诺里病基因突变检查。结果，两个鹿儿岛家族的外显子2的起始密码子发生了突变，东京的一个家族的外显子3发生了错义突变，千叶县的一个家族的基因发生了明显的复制。索尔斯比眼底营养不良(SFD SFD)是一种罕见的常染色体显性遗传性视网膜疾病，以成人发病和类似于年龄相关性黄斑变性的进行性眼底营养不良为特征。我们在鹿儿岛发现了两个患有SFD的家庭，这是日本和亚洲的第一个家庭。我们的两个家系被发现在内含子4/外显子5连接处有一个单核苷酸插入，这预示着SFD蛋白的截短。这种类型的突变在高加索人SFD患者中尚未报道，他们都在SED基因编码区的C末端显示错义突变。同样有趣的是，我们的日本患者在发病和疾病扩展方面与年龄相关性黄斑变性更为相似。先天性眼球震颤我们确定了一个以先天性眼球震颤、角膜畸形和中心凹发育不良为特征的四代家庭。疾病相关基因被定位在21号染色体上，对致病基因的搜索发现PAX6的配对区域存在错义突变。值得注意的是，我们的患者没有虹膜或葡萄膜组织的缺陷，尽管大多数PAX突变的患者表现为无虹膜。

This study dealt with molecular genetic analysis of important eye diseases. The main results are as follows.1. Norrie diseaseNorrie disease a rare X-linked disease that presents severe vitreoretinal dysplasia in infants. We had found previously two families in Kagoshima prefecture and during this study two additional families in Tokyo and Chiba. These four families were examined for mutations in the Norrie disease gene. As a result, two Kagoshima families had a mutation in the initiation codon of the exon 2, one family in Tokyo missense mutation in the exon 3, and one family in Chiba a gross duplication of the gene.2. Sorsby's fundus dystrophy (SFD SFD is a rare autosomal dominant retinal disease characterized by adult onset and progressive fundus dystrophy resembling age-related macular degeneration. We identified two families with SFD in Kagoshima, the first in Japan and Asia. Our two families were found to have a single nucleotide insertion in the intron4/exon 5 junction that predicted to truncate SFD protein. This type of mutation has not been reported in Caucasian SFD patients, who all showed missense mutations in the C-terminus of the coding region of the SED gene. It was also of interest that our Japanese patients were much more similar to age-related macular degeneration in its disease onset and extension of the disease.3. Congenital nystagmusWe identified a four-generation family featured by congenital nystagmus, corneal anomalies and foveal hypoplasia. The disease-associated gene was localized in chromosome 21, and a search for the causative gene has revealed a missense mutation in the paired domain of PAX6. It was remarkable that our patients had no defect in the iris or uveal tissue, although the majority of patients with PAX mutations present aniridia.