title: Identification of the Photoreceptor Transcriptional Co-Repressor SAMD11 as Novel Cause of Autosomal Recessive Retinitis Pigmentosa.
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.
authors.affiliation: Department of Genetics &Genomics, Health Research Institute-Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Corton
authors.affiliation: Department of Genetics &Genomics, Health Research Institute-Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Avila-Fernández
authors.affiliation: Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Campello
authors.affiliation: Department of Genetics &Genomics, Health Research Institute-Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sánchez
authors.affiliation: Department of Genetics &Genomics, Health Research Institute-Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Benavides
authors.affiliation: Department of Ophthalmology, Health Research Institute- Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.
authors.forename: M I
authors.initials: MI
authors.lastname: López-Molina
authors.affiliation: Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Fernández-Sánchez
authors.affiliation: Department of Genetics &Genomics, Health Research Institute-Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Sánchez-Alcudia
authors.affiliation: Department of Genetics &Genomics, Health Research Institute-Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.|Universidade de Mogi das Cruzes, São Paulo, Brazil.
authors.forename: L R J
authors.initials: LRJ
authors.lastname: da Silva
authors.affiliation: Department of Genetics &Genomics, Health Research Institute-Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Reyes
authors.affiliation: Department of Genetics &Genomics, Health Research Institute-Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Martín-Garrido
authors.affiliation: Department of Genetics &Genomics, Health Research Institute-Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Zurita
authors.affiliation: Department of Genetics &Genomics, Health Research Institute-Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Fernández-San José
authors.affiliation: Department of Genetics &Genomics, Health Research Institute-Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Pérez-Carro
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.|Bioinformatics in Rare Diseases (BIER), Centre for Biomedical Network Research on Rare Diseases (CIBERER), Valencia, Spain.
authors.forename: F
authors.initials: F
authors.lastname: García-García
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.|Bioinformatics in Rare Diseases (BIER), Centre for Biomedical Network Research on Rare Diseases (CIBERER), Valencia, Spain.|Functional Genomics Node (INB), Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: Department of Ophthalmology, Health Research Institute- Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: García-Sandoval
authors.affiliation: Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Cuenca
authors.affiliation: Department of Genetics &Genomics, Health Research Institute-Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Ayuso
mesh_terms: D000368:Aged; D000818:Animals; D056970:Co-Repressor Proteins / Q000378:metabolism; D018389:Codon, Nonsense; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D003241:Consanguinity; D004252:DNA Mutational Analysis; D059472:Exome; D005136:Eye Proteins / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005808:Genes, Recessive; D018398:Homeodomain Proteins / Q000378:metabolism*; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D025941:Protein Interaction Mapping; D012160:Retina / Q000378:metabolism / Q000503:physiopathology; D058499:Retinal Dystrophies / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D013030:Spain; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D056970:Co-Repressor Proteins; D018389:Codon, Nonsense; D005136:Eye Proteins; D018398:Homeodomain Proteins; C584612:SAMD11 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C109288:cone rod homeobox protein