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Sci Rep. 2016 Oct 13;6:35370. doi: 10.1038/srep35370.

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

Author information

1
Department of Genetics &Genomics, Health Research Institute-Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.
2
Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
3
Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
4
Department of Ophthalmology, Health Research Institute- Jiménez Díaz Foundation University Hospital (IIS-FJD), Madrid, Spain.
5
Universidade de Mogi das Cruzes, São Paulo, Brazil.
6
Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
7
Bioinformatics in Rare Diseases (BIER), Centre for Biomedical Network Research on Rare Diseases (CIBERER), Valencia, Spain.
8
Functional Genomics Node (INB), Valencia, Spain.

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.

PMID:
27734943
PMCID:
PMC5062157
DOI:
10.1038/srep35370
[Indexed for MEDLINE]
Free PMC Article

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