Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21
- PMID:10958649
- DOI: 10.1093/hmg/9.14.2107
Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21
Abstract
Achromatopsia is an autosomal recessive disorder featuring total colour blindness, photophobia, reduced visual acuity and nystagmus. While mutations in the CNGA3 gene on chromosome 2q11 are responsible for achromatopsia in a subset of patients, previous linkage studies have localized another achromatopsia locus, ACHM3, on chromosome 8q21. Using achromatopsia families in which CNGA3 mutations have been excluded, we refined the ACHM3 locus to a 3.7 cM region enclosed by markers D8S1838 and D8S273. Two yeast artificial chromosome (YAC) contigs covering nearly the entire ACHM3 interval were constructed. Database searches with YAC content sequences identified two overlapping high throughput genomic sequencing phase (HTGS) entries which contained sequences homologous to the murine cng6 gene encoding the putative beta-subunit of the cone photoreceptor cGMP-gated channel. Using RT-PCR and RACE, we identified and cloned the human cDNA homologue, designated CNGB3, which encodes an 809 amino acid polypeptide. Northern blot analysis revealed a major transcript of approximately 4.4 kb specifically expressed in the retina. The human CNGB3 gene consists of 18 exons distributed over approximately 200 kb of genomic sequence. Analysis of the CNGB3 gene in achromats revealed six different mutations including a missense mutation (S435F), two stop codon mutations (R203X and E336X), a 1 bp and an 8 bp deletion (1148delC and 819-826del) and a putative splice site mutation of intron 13. The 1148delC mutation was identified recurrently in several families, and in total was present on 11 of 22 disease chromosomes segregating in our families.
Similar articles
- Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3.Sidjanin DJ, Lowe JK, McElwee JL, Milne BS, Phippen TM, Sargan DR, Aguirre GD, Acland GM, Ostrander EA.Sidjanin DJ, et al.Hum Mol Genet. 2002 Aug 1;11(16):1823-33. doi: 10.1093/hmg/11.16.1823.Hum Mol Genet. 2002.PMID:12140185
- CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia.Kohl S, Varsanyi B, Antunes GA, Baumann B, Hoyng CB, Jägle H, Rosenberg T, Kellner U, Lorenz B, Salati R, Jurklies B, Farkas A, Andreasson S, Weleber RG, Jacobson SG, Rudolph G, Castellan C, Dollfus H, Legius E, Anastasi M, Bitoun P, Lev D, Sieving PA, Munier FL, Zrenner E, Sharpe LT, Cremers FP, Wissinger B.Kohl S, et al.Eur J Hum Genet. 2005 Mar;13(3):302-8. doi: 10.1038/sj.ejhg.5201269.Eur J Hum Genet. 2005.PMID:15657609
- Achromatopsia-associated mutation in the human cone photoreceptor cyclic nucleotide-gated channel CNGB3 subunit alters the ligand sensitivity and pore properties of heteromeric channels.Peng C, Rich ED, Varnum MD.Peng C, et al.J Biol Chem. 2003 Sep 5;278(36):34533-40. doi: 10.1074/jbc.M305102200. Epub 2003 Jun 18.J Biol Chem. 2003.PMID:12815043
- Achromatopsia: Genetics and Gene Therapy.Michalakis S, Gerhardt M, Rudolph G, Priglinger S, Priglinger C.Michalakis S, et al.Mol Diagn Ther. 2022 Jan;26(1):51-59. doi: 10.1007/s40291-021-00565-z. Epub 2021 Dec 3.Mol Diagn Ther. 2022.PMID:34860352Free PMC article.Review.
- Comprehensive variant spectrum of the CNGA3 gene in patients affected by achromatopsia.Solaki M, Baumann B, Reuter P, Andreasson S, Audo I, Ayuso C, Balousha G, Benedicenti F, Birch D, Bitoun P, Blain D, Bocquet B, Branham K, Català-Mora J, De Baere E, Dollfus H, Falana M, Giorda R, Golovleva I, Gottlob I, Heckenlively JR, Jacobson SG, Jones K, Jägle H, Janecke AR, Kellner U, Liskova P, Lorenz B, Martorell-Sampol L, Messias A, Meunier I, Belga Ottoni Porto F, Papageorgiou E, Plomp AS, de Ravel TJL, Reiff CM, Renner AB, Rosenberg T, Rudolph G, Salati R, Sener EC, Sieving PA, Stanzial F, Traboulsi EI, Tsang SH, Varsanyi B, Weleber RG, Zobor D, Stingl K, Wissinger B, Kohl S.Solaki M, et al.Hum Mutat. 2022 Jul;43(7):832-858. doi: 10.1002/humu.24371. Epub 2022 Apr 14.Hum Mutat. 2022.PMID:35332618Review.
Cited by
- Mutation of ATF6 causes autosomal recessive achromatopsia.Ansar M, Santos-Cortez RL, Saqib MA, Zulfiqar F, Lee K, Ashraf NM, Ullah E, Wang X, Sajid S, Khan FS, Amin-ud-Din M; University of Washington Center for Mendelian Genomics; Smith JD, Shendure J, Bamshad MJ, Nickerson DA, Hameed A, Riazuddin S, Ahmed ZM, Ahmad W, Leal SM.Ansar M, et al.Hum Genet. 2015 Sep;134(9):941-50. doi: 10.1007/s00439-015-1571-4. Epub 2015 Jun 11.Hum Genet. 2015.PMID:26063662Free PMC article.
- Network-based bioinformatics analysis of spatio-temporal RNA-Seq data reveals transcriptional programs underpinning normal and aberrant retinal development.Karunakaran DK, Al Seesi S, Banday AR, Baumgartner M, Olthof A, Lemoine C, Măndoiu II, Kanadia RN.Karunakaran DK, et al.BMC Genomics. 2016 Aug 31;17 Suppl 5(Suppl 5):495. doi: 10.1186/s12864-016-2822-z.BMC Genomics. 2016.PMID:27586787Free PMC article.
- Plasticity and stability of visual field maps in adult primary visual cortex.Wandell BA, Smirnakis SM.Wandell BA, et al.Nat Rev Neurosci. 2009 Dec;10(12):873-84. doi: 10.1038/nrn2741. Epub 2009 Nov 11.Nat Rev Neurosci. 2009.PMID:19904279Free PMC article.Review.
- A combined RNA-seq and whole genome sequencing approach for identification of non-coding pathogenic variants in single families.Bronstein R, Capowski EE, Mehrotra S, Jansen AD, Navarro-Gomez D, Maher M, Place E, Sangermano R, Bujakowska KM, Gamm DM, Pierce EA.Bronstein R, et al.Hum Mol Genet. 2020 Apr 15;29(6):967-979. doi: 10.1093/hmg/ddaa016.Hum Mol Genet. 2020.PMID:32011687Free PMC article.
- Potential contribution of ryanodine receptor 2 upregulation to cGMP/PKG signaling-induced cone degeneration in cyclic nucleotide-gated channel deficiency.Yang F, Ma H, Butler MR, Ding XQ.Yang F, et al.FASEB J. 2020 May;34(5):6335-6350. doi: 10.1096/fj.201901951RR. Epub 2020 Mar 16.FASEB J. 2020.PMID:32173907Free PMC article.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases