title: CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia.
abstract: Achromatopsia is a congenital, autosomal recessively inherited disorder characterized by a lack of color discrimination, low visual acuity (<0.2), photophobia, and nystagmus. Mutations in the genes for CNGA3, CNGB3, and GNAT2 have been associated with this disorder. Here, we analyzed the spectrum and prevalence of CNGB3 gene mutations in a cohort of 341 independent patients with achromatopsia. In 163 patients, CNGB3 mutations could be identified. A total of 105 achromats carried apparent homozygous mutations, 44 were compound (double) heterozygotes, and 14 patients had only a single mutant allele. The derived CNGB3 mutation spectrum comprises 28 different mutations including 12 nonsense mutations, eight insertions and/or deletions, five putative splice site mutations, and three missense mutations. Thus, the majority of mutations in the CNGB3 gene result in significantly altered and/or truncated polypeptides. Several mutations were found recurrently, in particular a 1 bp deletion, c.1148delC, which accounts for over 70% of all CNGB3 mutant alleles. In conclusion, mutations in the CNGB3 gene are responsible for approximately 50% of all patients with achromatopsia. This indicates that the CNGB3/ACHM3 locus on chromosome 8q21 is the major locus for achromatopsia in patients of European origin or descent.
authors.affiliation: Molekulargenetisches Labor, Universitäts-Augenklinik Tübingen, Abt. Pathophysiologie des Sehens und Neuroophthalmologie, Germany. susanne.kohl@uni-tuebingen.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Kohl
authors.forename: Balazs
authors.initials: B
authors.lastname: Varsanyi
authors.forename: Gesine Abadin
authors.initials: GA
authors.lastname: Antunes
authors.forename: Britta
authors.initials: B
authors.lastname: Baumann
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: Herbert
authors.initials: H
authors.lastname: Jägle
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenberg
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kellner
authors.forename: Birgit
authors.initials: B
authors.lastname: Lorenz
authors.forename: Roberto
authors.initials: R
authors.lastname: Salati
authors.forename: Bernhard
authors.initials: B
authors.lastname: Jurklies
authors.forename: Agnes
authors.initials: A
authors.lastname: Farkas
authors.forename: Sten
authors.initials: S
authors.lastname: Andreasson
authors.forename: Richard G
authors.initials: RG
authors.lastname: Weleber
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: Günther
authors.initials: G
authors.lastname: Rudolph
authors.forename: Claudio
authors.initials: C
authors.lastname: Castellan
authors.forename: Helene
authors.initials: H
authors.lastname: Dollfus
authors.forename: Eric
authors.initials: E
authors.lastname: Legius
authors.forename: Mario
authors.initials: M
authors.lastname: Anastasi
authors.forename: Pierre
authors.initials: P
authors.lastname: Bitoun
authors.forename: Dorit
authors.initials: D
authors.lastname: Lev
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
authors.forename: Francis L
authors.initials: FL
authors.lastname: Munier
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
authors.forename: Lindsay T
authors.initials: LT
authors.lastname: Sharpe
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
mesh_terms: D000483:Alleles; D000818:Animals; D003117:Color Vision Defects / Q000235:genetics* / Q000503:physiopathology / Q000662:veterinary; D054815:Cyclic Nucleotide-Gated Cation Channels; D004283:Dog Diseases / Q000235:genetics; D004285:Dogs; D005808:Genes, Recessive; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D017949:Retinal Cone Photoreceptor Cells
chemical_list: C415904:CNGB3 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels