Molecular genetic and pathophysiological study of new hereditary retinal diseases.

新遗传性视网膜疾病的分子遗传学和病理生理学研究。

• 批准号: 13307048
• 负责人: MIYAKE Yozo
• 金额: $ 30.2万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13307048/
• 关键词: Occult macular dystrophy; congenital stationary night blindness; complete type; incomplete type; ON bipolar cell; OFF bipolar cell; CACNAlF gene; NYX gene; APB; PDA; ERG; 遺伝性網膜疾患; 分子遺伝; 病態生理; 不全型先天停止性夜盲; 白点状眼底; CACNA1F遺伝子; RDH5遺伝子

"Occult macular dystrophy" is a new clinical entity detected by us and the clinical characteristics of 36 patients was studied. The autosomal dominant inheritance was suggested in 8 families. The visual acuity ranged from 0.1 to 1.0 and many patients showed red-green color vision deficiency. The fundi and fluorescein angiography were normal, however the detail analysis of OCT indicated that the thickness of the macula is significantly thinner than normal in many patients.We demonstrated that the congenital stationary night blindness with negative ERG is classified into two subtypes, complete and incomplete type, which are different clinical entities. Our hypothesis was proven true by molecular genetics. We studied 90 patients in terms of the molecular genetics and several visual functions. About half of the patients with complete type, the NYX gene mutation was shown, and all incomplete type patients showed CACNA1F gene mutation. The ERG findings indicated that the complete type has the selective dysfunction of the ON bipolar cell, while incomplete type has the incomplete dysfunction of both ON and OFF bipolar cells.Furthermore, the focal macular ERG recording, which we have developed suggested that the function of macula is different from other part of the retina in complete type. This result may be reasonable to explain that many patients show normal color vision and near normal contrast sensitivity in spite of the complete defect of ON visual pathway.

“隐匿性黄斑营养不良症”是美国检测到的一个新临床实体，研究了36例患者的临床特征。在8个家庭中提出了常染色体主导遗传。视力范围从0.1到1.0，许多患者表现出红绿色的色觉缺乏症。基础和荧光素血管造影是正常的，但是OCT的细节分析表明，在许多患者中，黄斑的厚度明显比正常情况明显薄。我们证明，先天性的夜间夜间失明，具有负ERG为两种亚型，是两种亚型，完全且不完整的类型，这些类型是不同的临床实验。分子遗传学证明了我们的假设是正确的。我们从分子遗传学和几种视觉功能方面研究了90例患者。大约一半具有完全类型的患者，显示了NYX基因突变，所有不完整的类型患者均显示CACNA1F基因突变。 ERG的发现表明，完整类型具有ON双极单元的选择性功能障碍，而不完整的类型的功能障碍不完整，但双极细胞的功能障碍。furthermore。焦点黄斑ERG记录，我们已经开发出的焦点黄斑ERG记录表明，黄斑的功能与整个视网膜的其他部分不同。这一结果可能是合理的，可以解释许多患者尽管完全缺陷视觉途径，但许多患者表现出正常的色觉和几乎正常的对比度灵敏度。

项目成果

Nakamura M, Ito S, Terasaki H, Miyake, Y: "Japanese X-linked juvenile retinoschisis : conflict of phenotype and genotype with novel mutations in the XLRS1 gene"Arch Ophthalmol. 119. 1553-1554 (2001)

Nakamura M、Ito S、Terasaki H、Miyake、Y：“日本 X 连锁青少年视网膜劈裂症：表型和基因型与 XLRS1 基因新突变的冲突”Arch Ophasemol。

Nakamura M, Ito S, Terasaki H, Miyake Y.: "Japanese X-linked juvenile retinoschisis : Conflict of phenotype : genotype with novel mutations in the XLRS1 gene"Arch Ophthalmol.. 119. 1553-1554 (2001)

Nakamura M、Ito S、Terasaki H、Miyake Y.：“日本 X 连锁青少年视网膜劈裂症：表型冲突：XLRS1 基因中具有新突变的基因型”Arch Ophthalmol.. 119. 1553-1554 (2001)

Horio N, Kachi S, Hori K, Terasaki H, Miyake Y, et al.: "Progressive change of optical coherence tomography scans in retinal degeneration slow (rds) mice"Arch Ophthalmol.. 119. 1329-1332 (2001)

Horio N、Kachi S、Hori K、Terasaki H、Miyake Y 等人：“视网膜变性缓慢 (rds) 小鼠中光学相干断层扫描的渐进变化”Arch Ophthalmol.. 119. 1329-1332 (2001)

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

Hotta Y、Nakamura M、Okamoto Y、Terasaki H、Miyake Y 等人：“XLRS1 基因的不同突变导致青少年视网膜劈裂伴视网膜白色斑点”Br J Ophthalmol.. 85. 238-239 (2001)

Nakamura M, Ito S, Terasaki H, Miyake Y: "Incomplete congenital stationary night blindness associated with symmetrical retinal atrophy"Am J Ophthalmol. 134. 463-465 (2002)

Nakamura M、Ito S、Terasaki H、Miyake Y：“与对称性视网膜萎缩相关的不完全先天性静止性夜盲症”Am J Ophamol。