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Identification of the Photoreceptor Transcriptional Co-Repressor SAMD11 as Novel Cause of Autosomal Recessive Retinitis Pigmentosa
- Source :
- Scientific Reports, SCIENTIFIC REPORTS, r-FISABIO. Repositorio Institucional de Producción Científica, instname, RUA. Repositorio Institucional de la Universidad de Alicante, Universidad de Alicante (UA), r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF), r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF), Centro de Investigación Principe Felipe (CIPF)
- Publication Year :
- 2016
-
Abstract
- Retinitis pigmentosa (RP), the most frequent form of inherited retinal dystrophy is characterized by progressive photoreceptor degeneration. Many genes have been implicated in RP development, but several others remain to be identified. Using a combination of homozygosity mapping, whole-exome and targeted next-generation sequencing, we found a novel homozygous nonsense mutation in SAMD11 in five individuals diagnosed with adult-onset RP from two unrelated consanguineous Spanish families. SAMD11 is ortholog to the mouse major retinal SAM domain (mr-s) protein that is implicated in CRX-mediated transcriptional regulation in the retina. Accordingly, protein-protein network analysis revealed a significant interaction of SAMD11 with CRX. Immunoblotting analysis confirmed strong expression of SAMD11 in human retina. Immunolocalization studies revealed SAMD11 was detected in the three nuclear layers of the human retina and interestingly differential expression between cone and rod photoreceptors was observed. Our study strongly implicates SAMD11 as novel cause of RP playing an important role in the pathogenesis of human degeneration of photoreceptors. This work was supported by several grants from the Spanish Centre for Biomedical Network Research on Rare Diseases (CIBERER)(06/07/0036), Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Health)/FEDER, including FIS (PI013/00226) and RETICS (RD09/0076/00101 and RD12/0034/0010), Ministry of Economy and Competitiveness (MINECO), including FEDER (BFU2012-36845), and BIO2011-27069, Conselleria de Educació of the Valencia Community (PROMETEOII/2014/025), Spanish National Organization of the Blind (ONCE) and the Spanish Fighting Blindness Foundation (FUNDALUCE). M.C. was sponsored by the Miguel Servet Program for Researchers in the Spanish National Health Service (CP12/03256) and RSA by Sara Borrel Postdoctoral Program (CD12/00676), both from the ISCIII/FEDER. A.A-F. was sponsored by CIBERER, RPC is supported by Fundación Conchita Rábago (FCR), L.C is sponsored by RETICS (RD12/0034/0010) from ISCIII and L.d.S. was supported by CAPES Foundation, Ministry of Education of Brazil.
- Subjects :
- 0301 basic medicine
Male
genetic structures
Autosomal recessive
DNA Mutational Analysis
Cohort Studies
chemistry.chemical_compound
Consanguinity
Mice
0302 clinical medicine
Photoreceptor degeneration
Retinal Rod Photoreceptor Cells
Protein Interaction Mapping
Transcriptional regulation
Exome
Genetics
Comparative Genomic Hybridization
Multidisciplinary
Gene therapy of the human retina
Homozygote
Middle Aged
Disease gene identification
Retinitis pigmentosa
medicine.anatomical_structure
Codon, Nonsense
Female
Co-Repressor Proteins
Retinitis Pigmentosa
SAMD11
Nonsense mutation
Genes, Recessive
Biology
Biología Celular
Polymorphism, Single Nucleotide
Retina
Article
03 medical and health sciences
Retinal Dystrophies
medicine
Animals
Humans
Eye Proteins
Gene
Aged
Homeodomain Proteins
Retinal
medicine.disease
030104 developmental biology
chemistry
Gene Expression Regulation
Spain
Trans-Activators
sense organs
030217 neurology & neurosurgery
Transcription Factors
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....964dbfc4b29fff273c7e1baf148f5ad2