Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis
- PMID: 16909394
- PMCID: PMC1559533
- DOI: 10.1086/507318
Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis
Abstract
Leber congenital amaurosis (LCA) is one of the main causes of childhood blindness. To date, mutations in eight genes have been described, which together account for approximately 45% of LCA cases. We localized the genetic defect in a consanguineous LCA-affected family from Quebec and identified a splice defect in a gene encoding a centrosomal protein (CEP290). The defect is caused by an intronic mutation (c.2991+1655A-->G) that creates a strong splice-donor site and inserts a cryptic exon in the CEP290 messenger RNA. This mutation was detected in 16 (21%) of 76 unrelated patients with LCA, either homozygously or in combination with a second deleterious mutation on the other allele. CEP290 mutations therefore represent one of the most frequent causes of LCA identified so far.
Figures
Similar articles
-
LEBER CONGENITAL AMAUROSIS DUE TO CEP290 MUTATIONS-SEVERE VISION IMPAIRMENT WITH A HIGH UNMET MEDICAL NEED: A Review.Retina. 2021 May 1;41(5):898-907. doi: 10.1097/IAE.0000000000003133. Retina. 2021. PMID: 33595255 Free PMC article. Review.
-
Antisense Oligonucleotide-Based Splicing Correction in Individuals with Leber Congenital Amaurosis due to Compound Heterozygosity for the c.2991+1655A>G Mutation in CEP290.Int J Mol Sci. 2018 Mar 7;19(3):753. doi: 10.3390/ijms19030753. Int J Mol Sci. 2018. PMID: 29518907 Free PMC article.
-
Unexpected CEP290 mRNA splicing in a humanized knock-in mouse model for Leber congenital amaurosis.PLoS One. 2013 Nov 6;8(11):e79369. doi: 10.1371/journal.pone.0079369. eCollection 2013. PLoS One. 2013. PMID: 24223178 Free PMC article.
-
Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype.Hum Mutat. 2007 Apr;28(4):416. doi: 10.1002/humu.9485. Hum Mutat. 2007. PMID: 17345604
-
[From gene to disease; Leber congenital amaurosis (LCA)].Ned Tijdschr Geneeskd. 2005 Oct 15;149(42):2334-7. Ned Tijdschr Geneeskd. 2005. PMID: 16261712 Review. Dutch.
Cited by
-
Retinal Ciliopathies and Potential Gene Therapies: A Focus on Human iPSC-Derived Organoid Models.Int J Mol Sci. 2024 Mar 1;25(5):2887. doi: 10.3390/ijms25052887. Int J Mol Sci. 2024. PMID: 38474133 Free PMC article. Review.
-
Spectrum of variants associated with inherited retinal dystrophies in Northeast Mexico.BMC Ophthalmol. 2024 Feb 12;24(1):60. doi: 10.1186/s12886-023-03276-7. BMC Ophthalmol. 2024. PMID: 38347443 Free PMC article.
-
The Clinical Findings, Pathogenic Variants, and Gene Therapy Qualifications Found in a Leber Congenital Amaurosis Phenotypic Spectrum Patient Cohort.Int J Mol Sci. 2024 Jan 19;25(2):1253. doi: 10.3390/ijms25021253. Int J Mol Sci. 2024. PMID: 38279252 Free PMC article.
-
iU-ExM: nanoscopy of organelles and tissues with iterative ultrastructure expansion microscopy.Nat Commun. 2023 Nov 30;14(1):7893. doi: 10.1038/s41467-023-43582-8. Nat Commun. 2023. PMID: 38036510 Free PMC article.
-
Molecular and functional correction of a deep intronic splicing mutation in CFTR by CRISPR-Cas9 gene editing.Mol Ther Methods Clin Dev. 2023 Oct 18;31:101140. doi: 10.1016/j.omtm.2023.101140. eCollection 2023 Dec 14. Mol Ther Methods Clin Dev. 2023. PMID: 38027060 Free PMC article.
References
Web Resources
-
- BDGP Splice Site Prediction by Neural Network, http://www.fruitfly.org/seq_tools/splice.html (for NNSPLICE version 0.9)
-
- Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for LCA and CEP290)
-
- RESCUE-ESE, http://genes.mit.edu/burgelab/rescue-ese/ (for prediction of exonic splice enhancers)
References
-
- Janecke AR, Thompson DA, Utermann G, Becker C, Hübner CA, Schmid E, McHenry CL, Nair AR, Rüschendorf F, Heckenlively J, Wissinger B, Nürnberg P, Gal A (2004) Mutations in RDH12 encoding a photoreceptor cell retinol dehydrogenase cause childhood-onset severe retinal dystrophy. Nat Genet 36:850–85410.1038/ng1394 - DOI - PubMed
-
- Bowne SJ, Sullivan LS, Mortimer SE, Hedstrom L, Zhu J, Spellicy CJ, Gire AI, Hughbanks-Wheaton D, Birch DG, Lewis RA, Heckenlively JR, Daiger SP (2006) Spectrum and frequency of mutations in IMPDH1 associated with autosomal dominant retinitis pigmentosa and Leber congenital amaurosis. Invest Ophthalmol Vis Sci 47:34–4210.1167/iovs.05-0868 - DOI - PMC - PubMed
-
- Hanein S, Perrault I, Gerber S, Tanguy G, Barbet F, Ducroq D, Calvas P, Dollfus H, Hamel C, Lopponen T, Munier F, Santos L, Shalev S, Zafeiriou D, Dufier J-L, Munnich A, Rozet J-M, Kaplan J (2004) Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis. Hum Mutat 23:306–31710.1002/humu.20010 - DOI - PubMed
-
- Zernant J, Kulm M, Dharmaraj S, den Hollander AI, Perrault I, Preising MN, Lorenz B, Kaplan J, Cremers FPM, Maumenee I, Koenekoop RK, Allikmets R (2005) Genotyping microarray (disease chip) for Leber congenital amaurosis: detection of modifier alleles. Invest Ophthalmol Vis Sci 46:3052–305910.1167/iovs.05-0111 - DOI - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials