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

Nat Genet. 2000 Nov;26(3):324-7. doi: 10.1038/81627.

Abstract

X-linked congenital stationary night blindness (XLCSNB) is characterized by impaired scotopic vision with associated ocular symptoms such as myopia, hyperopia, nystagmus and reduced visual acuity. Genetic mapping in families with XLCSNB revealed two different loci on the proximal short arm of the X chromosome. These two genetic subtypes can be distinguished on the basis of electroretinogram (ERG) responses and psychophysical testing as a complete (CSNB1) and an incomplete (CSNB2) form. The CSNB1 locus has been mapped to a 5-cM linkage interval in Xp11.4 (refs 2,5-7). Here we construct and analyse a contig between the markers DXS993 and DXS228, leading to the identification of a new gene mutated in CSNB1 patients. It is partially deleted in 3 families and mutation analysis in a further 21 families detected another 13 different mutations. This gene, designated NYX, encodes a protein of 481 amino acids (nyctalopin) and is expressed at low levels in tissues including retina, brain, testis and muscle. The predicted polypeptide is 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 superfamily are involved in cell adhesion and axon guidance. Future functional analysis of nyctalopin might therefore give insight into the fine-regulation of cell-cell contacts in the retina.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Brain / metabolism
  • Chromosome Mapping
  • DNA Mutational Analysis
  • DNA, Complementary / genetics
  • Electroretinography
  • Eye Proteins / chemistry
  • Eye Proteins / genetics*
  • Eye Proteins / physiology
  • Female
  • Gene Expression Profiling
  • Genes*
  • Genetic Heterogeneity
  • Genetic Markers
  • Glycosylphosphatidylinositols / metabolism
  • Humans
  • Kidney / metabolism
  • Leucine / analysis
  • Male
  • Models, Molecular
  • Molecular Sequence Data
  • Multigene Family
  • Muscle Proteins / biosynthesis
  • Muscle Proteins / genetics
  • Muscles / metabolism
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Night Blindness / classification
  • Night Blindness / genetics*
  • Organ Specificity
  • Pedigree
  • Protein Conformation
  • Proteoglycans / chemistry
  • Proteoglycans / deficiency
  • Proteoglycans / genetics*
  • Proteoglycans / physiology
  • Repetitive Sequences, Amino Acid
  • Retina / metabolism
  • Retina / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Testis / metabolism
  • X Chromosome / genetics*

Substances

  • DNA, Complementary
  • Eye Proteins
  • Genetic Markers
  • Glycosylphosphatidylinositols
  • Muscle Proteins
  • NYX protein, human
  • Nerve Tissue Proteins
  • Proteoglycans
  • Leucine

Associated data

  • GENBANK/AA864288
  • GENBANK/AF032119
  • GENBANK/AF039686
  • GENBANK/AF061337
  • GENBANK/AJ278865
  • GENBANK/AL133329
  • GENBANK/AL136166
  • GENBANK/X98296
  • GENBANK/Z92545
  • GENBANK/Z93015
  • GENBANK/Z93403
  • GENBANK/Z94277