Analysis of the PRPF31 Gene in Spanish Autosomal Dominant Retinitis Pigmentosa Patients: A Novel Genomic Rearrangement
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Le résumé fourni par la source
Purpose: The aim was to determine the prevalence of PRPF31 mutations in a cohort of Spanish autosomal dominant retinitis pigmentosa (adRP) families to deepen knowledge of the pathogenic mechanisms underlying the disease and to assess genotype-phenotype correlations. Methods: A cohort of 211 adRP patients was screened for variants in PRPF31 by using a combined strategy comprising next-generation sequencing approaches and copy-number variation (CNV) analysis. Quantitative RT-PCR and CNV analysis of the regulatory MSR1 element were also performed to assess PRPF31 gene expression. Phenotype was assessed by using ophthalmologic examination protocols. Results: Fifteen different causative mutations and genomic rearrangements were identified, revealing five novel mutations. Prevalence of PRPF31 mutations, genomic rearrangements, and lack of penetrance were 7.6%, 1.9%, and 66.7%, respectively. Interestingly, we identified a tandem duplication and a partial PRPF31 deletion in different affected individuals from the same family. PRPF31 gene expression was significantly decreased in symptomatic cases carrying either PRPF31 duplication or deletion as compared to controls. The 4 MSR1 allele in cis with the PRPF31 wild-type allele was apparently a protective factor. The mutated phenotype varied from no symptoms to typical retinitis pigmentosa with variable onset and course depending on the kind of mutation, with the duplication case the most severe. Conclusions: In view of the high genetic heterogeneity of PRPF31 mutations, the screening must include the entire gene, as well as CNV assays, to detect large rearrangements. This is the first report of a variable phenotype correlation as well as a gross duplication and deletion within the same family.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Analysis of the <i>PRPF31</i> Gene in Spanish Autosomal Dominant Retinitis Pigmentosa Patients: A Novel Genomic Rearrangement
- Date Crossref
- 13/02/2017
- Éditeur
- Association for Research in Vision and Ophthalmology (ARVO)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Instituto de Salud Carlos III pays non établi dans la noticeOrganisme public
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Centre for Biomedical Network Research on Rare Diseases pays non établi dans la noticeStructure de recherche
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Universidad Autónoma de Madrid Department of Genetics pays non établi dans la noticeUniversité ou école supérieure
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Universidade de Mogi das Cruzes pays non établi dans la noticeUniversité ou école supérieure
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Children's Hospital of Philadelphia Center for Applied Genomics pays non établi dans la noticeOrganisme public
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Hospital Universitario Fundación Jiménez Díaz pays non établi dans la noticeÉtablissement de santé
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Hospital Terrassa pays non établi dans la noticeÉtablissement de santé
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Hospital de Terrassa Molecular Genetics Unit pays non établi dans la noticeÉtablissement de santé
Instituto de Salud Carlos III, Centre for Biomedical Network Research on Rare Diseases et Department of Genetics — Universidad Autónoma de Madrid, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.