Bech-Hansen N T, Naylor M J, Maybaum T A, Sparkes R L, Koop B, Birch D G, Bergen A A, Prinsen C F, Polomeno R C, Gal A, Drack A V, Musarella M A, Jacobson S G, Young R S, Weleber R G
Department of Medical Genetics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Nat Genet. 2000 Nov;26(3):319-23. doi: 10.1038/81619.
During development, visual photoreceptors, bipolar cells and other neurons establish connections within the retina enabling the eye to process visual images over approximately 7 log units of illumination. Within the retina, cells that respond to light increment and light decrement are separated into ON- and OFF-pathways. Hereditary diseases are known to disturb these retinal pathways, causing either progressive degeneration or stationary deficits. Congenital stationary night blindness (CSNB) is a group of stable retinal disorders that are characterized by abnormal night vision. Genetic subtypes of CSNB have been defined and different disease actions have been postulated. The molecular bases have been elucidated in several subtypes, providing a better understanding of the disease mechanisms and developmental retinal neurobiology. Here we have studied 22 families with 'complete' X-linked CSNB (CSNB1; MIM 310500; ref. 4) in which affected males have night blindness, some photopic vision loss and a defect of the ON-pathway. We have found 14 different mutations, including 1 founder mutation in 7 families from the United States, in a novel candidate gene, NYX. NYX, which encodes a glycosylphosphatidyl (GPI)-anchored protein called nyctalopin, is a new and unique member of the small leucine-rich proteoglycan (SLRP) family. The role of other SLRP proteins suggests that mutant nyctalopin disrupts developing retinal interconnections involving the ON-bipolar cells, leading to the visual losses seen in patients with complete CSNB.
在发育过程中，视觉光感受器、双极细胞和其他神经元在视网膜内建立连接，使眼睛能够在大约7个对数单位的光照范围内处理视觉图像。在视网膜内，对光增强和光减弱做出反应的细胞被分为ON通路和OFF通路。已知遗传性疾病会干扰这些视网膜通路，导致进行性退化或静止性缺陷。先天性静止性夜盲（CSNB）是一组以异常夜视为特征的稳定视网膜疾病。CSNB的遗传亚型已被定义，并推测了不同的疾病作用机制。在几个亚型中已经阐明了分子基础，这有助于更好地理解疾病机制和视网膜发育神经生物学。在这里，我们研究了22个患有“完全性”X连锁CSNB（CSNB1；MIM 310500；参考文献4）的家系，其中受影响的男性患有夜盲症、一些明视觉丧失以及ON通路缺陷。我们在一个新的候选基因NYX中发现了14种不同的突变，其中包括在美国7个家系中发现的1个奠基者突变。NYX编码一种名为夜盲蛋白的糖基磷脂酰肌醇（GPI）锚定蛋白，是富含亮氨酸小分子蛋白聚糖（SLRP）家族中的一个新的独特成员。其他SLRP蛋白的作用表明，突变的夜盲蛋白会破坏涉及ON双极细胞的视网膜发育互连，导致完全性CSNB患者出现视觉丧失。
