Molecular genetic analysis of hereditary retinal diseases

遗传性视网膜疾病的分子遗传学分析

• 批准号: 12671703
• 负责人: NAKAMURA Makoto
• 金额: $ 2.62万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671703/
• 关键词: hereditary retinal diseases; molecular genetics; X-linkedjuvenile retinoschisis; fundus albipunctatus; incomplete congenital stationary night blindness; RDH5 gene; XLRS1 gene; CACNA1F gene

The phenotypes of hereditary eye diseases are heterogeneous, and it was difficult to diagnose some cases whose clinical features were atypical. Recent advances in molecular genetics enabled us to diagnose such cases, presenting new information about phenotypic variations of the diseases.Fundus albipunctatus has been considered to be a stationary disorder with night blindness, with normal visual acuity, visual field and color perception. However, we have examined RDH5 gene, the causing gene of fundus albipunctatus, and revealed that many patients with fundus albipunctatus develop cone dystrophy with age resulting in progressive decline of visual functions. Furthermore, we have shown a child case with fundus albipunctatus accompanied with macular dystrophy and reduced uncorrectable visual acuity. These findings have changed the concept of the disease.X-linked juvenile retinoschisis (XRS) is a vitreoretinal dystrophy that is characterized by a tangential splitting of the superficial layer … More s of the sensory retina and an abnormal negative configuration in electroretinogram. We examined the XLRS1 gene, the causing gene of XRS, and showed that some cases with XRS presented white punctata in the retina. Also, we revealed that some cases with macular degeneration associated with negative electroretinogram were affected by XRS. Moreover, we found that some cases with XRS did not show the negative configuration but a normal shape in electroretinogram.Incomplete type of congenital stationary night blindness (CSNB) characterized by negative electroretinogram, normal fundi, and normal visual field was first reported from our university. We examined the CACNA1F gene, the recently identified causing gene of incomplete CSNB, and detected mutations in all of the cases. Furthermore, we found some atypical cases accompanied with retinal degeneration and visual field defects.We also identified the genetic causes of other retinal or corneal diseases, and obtained many novel results about the genotypes and phenotypes of the diseases. Less

遗传性眼病的表型具有异质性，一些临床特征不典型的病例很难诊断，分子遗传学的最新进展使我们能够诊断此类病例，提供了有关疾病表型变异的新信息。是一种患有夜盲症的静止性疾病，视力、视野和色觉都正常。但是，我们检查了白斑眼底症的致病基因 RDH5 基因，结果发现：许多眼底白斑患者随着年龄的增长会出现视锥细胞营养不良，导致视功能进行性下降。此外，我们还发现了一个伴有黄斑营养不良和不可矫正视力下降的儿童病例。这些发现改变了这种疾病的概念。连锁青少年视网膜劈裂 (XRS) 是一种玻璃体视网膜营养不良，其特征是感觉表面层的切向分裂……更多我们检查了 XRS 的致病基因 XLRS1 基因，发现一些 XRS 病例的视网膜出现白色点状。此外，我们还发现一些与视网膜电图阴性相关的黄斑变性病例。此外，我们发现一些XRS病例在视网膜电图上不显示阴性构型，而是显示正常形状。不完全型先天性静止性夜盲症（CSNB）的特征为阴性。视网膜电图、眼底正常、视野正常是我校首次报道的，我们对最近发现的不完全CSNB的致病基因CACNA1F基因进行了检查，并在所有病例中发现了一些不典型的病例。我们还鉴定了其他视网膜或角膜疾病的遗传原因，并获得了许多关于这些疾病的基因型和表型的新结果。

项目成果

Hotta Y,Nakamura M,Okamoto Y,Nomura R,Terasaki H,Miyake Y.: "Different mutation of the XLRS1 gene causes juvenile retinoschisis with retinal white flecks."Br J Ophthalmol.. Feb;85(2). 238-239 (2001)

Hotta Y、Nakamura M、Okamoto Y、Nomura R、Terasaki H、Miyake Y.：“XLRS1 基因的不同突变导致青少年视网膜劈裂并伴有视网膜白色斑点。”Br J Ophamol.. Feb；85(2)。

Terasaki H, Miyake Y, Suzuki T, Niwa T, Nakamura M, et al.: "Change in full-Field ERGs after macular translocation surgery with 360 retinotomy"Invest Ophthalmol Vis Sci.. 43. 452-457 (2002)

Terasaki H、Miyake Y、Suzuki T、Niwa T、Nakamura M 等人：“360 度视网膜切开术黄斑移位手术后全视野 ERG 的变化”Invest Ophasemol Vis Sci.. 43. 452-457 (2002)

Nakamura M, Singh DP, Kubo E, Chylack LT, Shinohara T.: "LEDGF : survival of embryonic chick retinal photoreceptor cells"Invest Ophthalmol Vis Sci.. 41. 1168-1175 (2000)

Nakamura M、Singh DP、Kubo E、Chylack LT、Shinohara T.：“LEDGF：胚胎鸡视网膜感光细胞的存活”Invest Ophasemol Vis Sci.. 41. 1168-1175 (2000)

Nakamura M: "Hereditary retinal disease and genome medicine"Journal of the Eye. 18. 1505-1507 (2001)

Nakamura M：《遗传性视网膜疾病和基因组医学》《眼科杂志》。

平野耕治, 中村 誠, 山本憲明, 堀田喜裕: "愛知県の格子状角膜ジストロフィ患者の地域特性:TGFBI遺伝子変異の検討"日眼会誌. 108(印刷中). (2001)

Koji Hirano、Makoto Nakamura、Noriaki Yamamoto、Yoshihiro Hotta：“爱知县格子状角膜营养不良患者的区域特征：TGFBI 基因突变的检查”日本眼科协会杂志 108（出版中）。