title: Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness.
abstract: 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.
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. ntbech@ucalgary.ca
authors.forename: N T
authors.initials: NT
authors.lastname: Bech-Hansen
authors.forename: M J
authors.initials: MJ
authors.lastname: Naylor
authors.forename: T A
authors.initials: TA
authors.lastname: Maybaum
authors.forename: R L
authors.initials: RL
authors.lastname: Sparkes
authors.forename: B
authors.initials: B
authors.lastname: Koop
authors.forename: D G
authors.initials: DG
authors.lastname: Birch
authors.forename: A A
authors.initials: AA
authors.lastname: Bergen
authors.forename: C F
authors.initials: CF
authors.lastname: Prinsen
authors.forename: R C
authors.initials: RC
authors.lastname: Polomeno
authors.forename: A
authors.initials: A
authors.lastname: Gal
authors.forename: A V
authors.initials: AV
authors.lastname: Drack
authors.forename: M A
authors.initials: MA
authors.lastname: Musarella
authors.forename: S G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: R S
authors.initials: RS
authors.lastname: Young
authors.forename: R G
authors.initials: RG
authors.lastname: Weleber
mesh_terms: D000328:Adult; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D020224:Expressed Sequence Tags; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling; D005796:Genes; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D007395:Interneurons / Q000378:metabolism / Q000473:pathology*; D007668:Kidney / Q000378:metabolism; D007930:Leucine / Q000032:analysis; D008297:Male; D008969:Molecular Sequence Data; D009755:Night Blindness / Q000145:classification / Q000235:genetics*; D009928:Organ Specificity; D010375:Pedigree; D011509:Proteoglycans / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D020449:Repetitive Sequences, Amino Acid; D012160:Retina / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D009435:Synaptic Transmission / Q000502:physiology; D014785:Vision, Ocular / Q000502:physiology; D014960:X Chromosome / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D005136:Eye Proteins; D017261:Glycosylphosphatidylinositols; C416505:NYX protein, human; D011509:Proteoglycans; D007930:Leucine