The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein

X-linked congenital stationary night blindness (XLCSNB) is characterized by impaired scotopic Vision with associated ocular symptoms such as myopia, h yperopia, nystagmus and reduced visual acuity(1). Genetic mapping in famili es with XLCSNB revealed two different loci on the proximal short arm of the X chromosome(2). These two genetic subtypes can be distinguished on the ba sis of electroretinogram (ERG) responses and psychophysical testing as a co mplete (CSNB1) and an incomplete (CSNB2) form(3,4). The CSNB1 locus has bee n mapped to a 5-cM linkage interval in Xp11.4 (refs 2,5-7). Here we constru ct and analyse a contig between the markers DXS993 and DXS228, leading to t he identification of a new gene mutated in CSNB1 patients. It is partially deleted in 3 families and mutation analysis in a further 21 families detect ed another 13 different mutations. This gene, designated NYX, encodes a pro tein of 481 amino acids (nyctalopin) and is expressed at low levels in tiss ues including retina, brain, testis and muscle. The predicted polypeptide i s a glycosylphosphatidylinositol (GPI)-anchored extracellular protein with 11 typical and 2 cysteine-rich, leucine-rich repeats (LRRs). This motif is important for protein-protein interactions and members of the LRR superfami ly are involved in cell adhesion and axon guidance(8-10). Future functional analysis of nyctalopin might therefore give insight into the fine-regulati on of cell-cell contacts in the retina.