title: Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosa.
abstract: Inherited retinal diseases are a common cause of visual impairment in children and young adults, often resulting in severe loss of vision in later life. The most frequent form of inherited retinopathy is retinitis pigmentosa (RP), with an approximate incidence of 1 in 3,500 individuals worldwide. RP is characterized by night blindness and progressive degeneration of the midperipheral retina, accompanied by bone spicule-like pigmentary deposits and a reduced or absent electroretinogram (ERG). The disease process culminates in severe reduction of visual fields or blindness. RP is genetically heterogeneous, with autosomal dominant, autosomal recessive and X-linked forms. Here we have identified two mutations in a novel retina-specific gene from chromosome 8q that cause the RP1 form of autosomal dominant RP in three unrelated families. The protein encoded by this gene is 2,156 amino acids and its function is currently unknown, although the amino terminus has similarity to that of the doublecortin protein, whose gene (DCX) has been implicated in lissencephaly in humans. Two families have a nonsense mutation in codon 677 of this gene (Arg677stop), whereas the third family has a nonsense mutation in codon 679 (Gln679stop). In one family, two individuals homozygous for the mutant gene have more severe retinal disease compared with heterozygotes.
authors.affiliation: Human Genetics Center, School of Public Health, and Department of Ophthalmology and Visual Science, The University of Texas Health Science Center, Houston 77030, USA. gsbs047@utsph.sph.uth.tmc.edu
authors.forename: L S
authors.initials: LS
authors.lastname: Sullivan
authors.forename: J R
authors.initials: JR
authors.lastname: Heckenlively
authors.forename: S J
authors.initials: SJ
authors.lastname: Bowne
authors.forename: J
authors.initials: J
authors.lastname: Zuo
authors.forename: W A
authors.initials: WA
authors.lastname: Hide
authors.forename: A
authors.initials: A
authors.lastname: Gal
authors.forename: M
authors.initials: M
authors.lastname: Denton
authors.forename: C F
authors.initials: CF
authors.lastname: Inglehearn
authors.forename: S H
authors.initials: SH
authors.lastname: Blanton
authors.forename: S P
authors.initials: SP
authors.lastname: Daiger
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002648:Child; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D012160:Retina / Q000378:metabolism*; D012174:Retinitis Pigmentosa / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D005136:Eye Proteins; D008869:Microtubule-Associated Proteins; C120042:RP1 protein, human