Discovery and functional analysis of a retinitis pigmentosa gene, C2ORF71

Darryl Y Nishimura; Lisa M Baye; Rahat Perveen; Charles C Searby; Almudena Avila-Fernandez; Ines Pereiro; Carmen Ayuso; Diana Valverde; Paul N Bishop; Forbes D C Manson; Jill Urquhart; Edwin M Stone; Diane C Slusarski; Graeme C M Black; Val C Sheffield

doi:10.1016/j.ajhg.2010.03.005

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Discovery and functional analysis of a retinitis pigmentosa gene, C2ORF71

Journal article

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Discovery and functional analysis of a retinitis pigmentosa gene, C2ORF71

Darryl Y Nishimura, Lisa M Baye, Rahat Perveen, Charles C Searby, Almudena Avila-Fernandez, Ines Pereiro, Carmen Ayuso, Diana Valverde, Paul N Bishop, Forbes D C Manson, …

American journal of human genetics, Vol.86(5), pp.686-695

05/14/2010

DOI: 10.1016/j.ajhg.2010.03.005

PMCID: PMC2868997

PMID: 20398886

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Abstract

Retinitis pigmentosa is a genetically heterogeneous group of inherited ocular disorders characterized by progressive photoreceptor cell loss, night blindness, constriction of the visual field, and progressive visual disability. Homozygosity mapping and gene expression studies identified a 2 exon gene, C2ORF71. The encoded protein has no homologs and is highly expressed in the eye, where it is specifically expressed in photoreceptor cells. Two mutations were found in C2ORF71 in human RP patients: A nonsense mutation (p.W253X) in the first exon is likely to be a null allele; the second, a missense mutation (p.I201F) within a highly conserved region of the protein, leads to proteosomal degradation. Bioinformatic and functional studies identified and validated sites of lipid modification within the first three amino acids of the C2ORF71 protein. Using morpholino oligonucleotides to knockdown c2orf71 expression in zebrafish results in visual defects, confirming that C2ORF71 plays an important role in the development of normal vision. Finally, localization of C2ORF71 to primary cilia in cultured cells suggests that the protein is likely to localize to the connecting cilium or outer segment of photoreceptor cells.

Eye - metabolism

Exons

Humans

Retinitis Pigmentosa - genetics

Retinitis Pigmentosa - metabolism

Mutation, Missense

Blindness - genetics

Cilia - metabolism

Cilia - genetics

Proteins - genetics

Homozygote

Eye Proteins - genetics

Mutation

Photoreceptor Cells, Vertebrate - metabolism

Details

Title: Subtitle: Discovery and functional analysis of a retinitis pigmentosa gene, C2ORF71
Creators: Darryl Y Nishimura - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Lisa M Baye
Rahat Perveen
Charles C Searby
Almudena Avila-Fernandez
Ines Pereiro
Carmen Ayuso
Diana Valverde
Paul N Bishop
Forbes D C Manson
Jill Urquhart
Edwin M Stone
Diane C Slusarski
Graeme C M Black
Val C Sheffield
Resource Type: Journal article
Publication Details: American journal of human genetics, Vol.86(5), pp.686-695
DOI: 10.1016/j.ajhg.2010.03.005
PMID: 20398886
PMCID: PMC2868997
NLM abbreviation: Am J Hum Genet
ISSN: 0002-9297
eISSN: 1537-6605
Publisher: United States
Grant note: T32 HL007121 / NHLBI NIH HHS R EY110298 / NEI NIH HHS Howard Hughes Medical Institute R EY017168 / NEI NIH HHS R01 CA112369 / NCI NIH HHS R01 EY017168 / NEI NIH HHS
Language: English
Date published: 05/14/2010
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Biology; Ophthalmology and Visual Sciences
Record Identifier: 9983980050302771

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