OR2W3 sequence variants are unlikely to cause inherited retinal diseases.

Details

Serval ID
serval:BIB_2C2076D00973
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
OR2W3 sequence variants are unlikely to cause inherited retinal diseases.
Journal
Ophthalmic genetics
Author(s)
Sharon D., Kimchi A., Rivolta C.
ISSN
1744-5094 (Electronic)
ISSN-L
1381-6810
Publication state
Published
Issued date
12/2016
Peer-reviewed
Oui
Volume
37
Number
4
Pages
366-368
Language
english
Abstract
Because of its formidable throughput, whole exome sequencing (WES) is significantly increasing the power of investigations in ophthalmic genetics. However, when applied to Mendelian conditions, WES results often contain many false positives, e.g. candidate mutations that are unrelated to the disease. For instance, highly polymorphic genes such as olfactory receptor genes carry a plethora of both common and rare alleles that are part of the normal set of variations of the human genome. Following a WES-based study, the heterozygous missense variant p.R142W in the olfactory receptor gene OR2W3 was recently reported as a pathogenic mutation causing autosomal dominant retinitis pigmentosa (RP). This variant, however, was not scored against data contained in public WES repositories, indicating that p.R142W is present in ~1 in 6500 control individuals. Therefore, if it really was pathogenic, it would be responsible for a percentage of dominant RP cases corresponding to the double of those recorded so far worldwide, or 2/3 of all RP cases (dominant, recessive, and X-linked). We therefore conclude that this sequence variant, and hence the OR2W3 gene, do not cause RP. Prompted by these findings and based on simple principles of population genetics, we suggest that WES studies should consider DNA variants as the possible cause of dominant RP only if they are present in less than 1:100,000 individuals from the general population. In addition, we propose that DNA variants belonging to highly polymorphic genes should be carefully analyzed at the functional level before inferring their pathogenicity, in RP or other genetic diseases.

Keywords
Child Development, Cognition, Cohort Studies, Female, Humans, Infant, Newborn, Infant, Premature/growth & development, Infant, Small for Gestational Age/growth & development, Male, Neurodevelopmental Disorders/epidemiology
Pubmed
Create date
16/02/2016 17:48
Last modification date
20/08/2019 13:11
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