Identification of the Photoreceptor Transcriptional Co-Repressor SAMD11 as Novel Cause of Autosomal Recessive Retinitis Pigmentosa.

TitleIdentification of the Photoreceptor Transcriptional Co-Repressor SAMD11 as Novel Cause of Autosomal Recessive Retinitis Pigmentosa.
Publication TypeJournal Article
Year of Publication2016
AuthorsCorton, M, Avila-Fernández, A, Campello, L, Sánchez, M, Benavides, B, López-Molina, MI, Fernández-Sánchez, L, Sánchez-Alcudia, R, da Silva, LRJ, Reyes, N, Martín-Garrido, E, Zurita, O, P San José, F-, Pérez-Carro, R, García-García, F, Dopazo, J, García-Sandoval, B, Cuenca, N, Ayuso, C
JournalSci Rep
Date Published2016 10 13
KeywordsAged; Animals; Co-Repressor Proteins; Codon, Nonsense; Cohort Studies; Comparative Genomic Hybridization; Consanguinity; DNA Mutational Analysis; Exome; Eye Proteins; Female; Gene Expression Regulation; Genes, Recessive; Homeodomain Proteins; Homozygote; Humans; Male; Mice; Middle Aged; Polymorphism, Single Nucleotide; Protein Interaction Mapping; Retina; Retinal Dystrophies; Retinal Rod Photoreceptor Cells; Retinitis pigmentosa; Spain; Trans-Activators; Transcription Factors

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.

Alternate JournalSci Rep
PubMed ID27734943
PubMed Central IDPMC5062157