Duda Teresa, Koch Karl-Wilhelm
Department of Cell Biology, SOM and NJMS, University of Medicine and Dentistry of New Jersey, Stratford 08084, USA.
Mol Cell Biochem. 2002 Jan;230(1-2):129-38.
Inherited retinal dystrophies are the main causes of progressive visual impairment often leading to blindness. They represent a clinically and genetically heterogenous group of disorders. Continuously increasing body of evidence links retinal dystrophies to mutations in numerous genes. These genes code for retinal proteins of various function (phototransduction, visual cycle, transcription factors, structural and metabolic functions). Mutations in the gene coding for photoreceptor specific guanylate cyclase type 1, ROS-GC1, were found to be the cause for the type 1 Leber's congenital amaurosis (LCAI) and cone-rod dystrophy type 6 (CORD6). The LCA1-linked mutations are distributed over almost the entire ROS-GCI coding sequence but the CORD6-linked mutations are restricted to three positions, E786, R787 and T788, located within the putative ROS-GC1 dimerization domain. A linkage between the biochemical effect of the mutation and its phenotypic manifestation was provided for only one LCA1 mutation, F514S. This was followed by biochemical analyses of the consequences of the CORD6-causing mutations. Here, an overview on the existing results and a discussion of the possible physiological implications are presented.
遗传性视网膜营养不良是导致进行性视力损害并常常导致失明的主要原因。它们代表了一组临床和遗传异质性疾病。越来越多的证据表明视网膜营养不良与众多基因的突变有关。这些基因编码具有各种功能的视网膜蛋白（光转导、视觉循环、转录因子、结构和代谢功能）。已发现编码光感受器特异性鸟苷酸环化酶1（ROS-GC1）的基因突变是1型莱伯先天性黑蒙（LCAI）和6型锥杆营养不良（CORD6）的病因。与LCA1相关的突变几乎分布在整个ROS-GCI编码序列上，但与CORD6相关的突变仅限于位于假定的ROS-GC1二聚化结构域内的三个位置，即E786、R787和T788。仅针对一种LCA1突变F514S提供了突变的生化效应与其表型表现之间的联系。随后对导致CORD6的突变后果进行了生化分析。在此，对现有结果进行概述并讨论可能的生理意义。
