December 2015
Volume 56, Issue 13
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Letters to the Editor  |   December 2015
Further Consideration of the Association Between OR2W3 Mutation and Retinitis Pigmentosa
Author Affiliations & Notes
  • Di Zhang
    Department of Coloproctology the Sixth Affiliated Hospital of Sun Yat-sen University (Gastrointestinal & Anal Hospital), Guangzhou, China; and
  • Xiaobo Huang
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Investigative Ophthalmology & Visual Science December 2015, Vol.56, 8028. doi:10.1167/iovs.15-18142
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      Di Zhang, Xiaobo Huang; Further Consideration of the Association Between OR2W3 Mutation and Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2015;56(13):8028. doi: 10.1167/iovs.15-18142.

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      © ARVO (1962-2015); The Authors (2016-present)

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We read with interest the article entitled “Whole-exome sequencing identifies OR2W3 mutation as a cause of autosomal dominant retinitis pigmentosa” by Ma et al.,1 who described a novel missense mutation (c.C424T/p.R142W) in OR2W3 as a potentially causative mutation for autosomal dominant retinitis pigmentosa (RP) in two Chinese families. 
Retinitis pigmentosa is an inherited retinal disease with an incidence of approximately 1 in every 3000 to 5000 people.2,3 Due to the rarity of RP, the frequency of a high-penetrance mutation associated with autosomal dominant RP should be very low in the general population, and should certainly not exceed the incidence of RP. However, the variant (rs189993261, c.C424T/p.R142W in OR2W3) has been reported to have a minor allele frequency of 2/1008 and 4/8652 in East Asians in the 1000 Genomes Project database4 and Exome Aggregation Consortium (ExAC) database,5 respectively. The minor allele frequency of the variant in Chinese (1/206, 0.005) has been reported to reach the threshold of low-frequency variants in the 1000 Genomes Project database.4 The region with the p.R142W variant is not conserved in mammals (see Figure). Further, computational prediction of the variant using dbNSFP database does not support it as a deleterious mutation (see Table).6 
Figure
 
Protein sequence alignment of seven OR2W3 orthologs shows that the region with the variant (p.R142W) is not conserved.
Figure
 
Protein sequence alignment of seven OR2W3 orthologs shows that the region with the variant (p.R142W) is not conserved.
Table
 
Functional Prediction of c.C424T/p.R142W in OR2W3
Table
 
Functional Prediction of c.C424T/p.R142W in OR2W3
The results of allele frequency, protein conservation, and bioinformatics analyses suggest that the variant (rs189993261, c.C424T/p.R142W) in OR2W3 is likely to be a single nucleotide polymorphism, but that it is not causative on its own. Although the variant has been reported to be cosegregated with RP in a large Chinese family, 1 the possibility of linkage disequilibrium between the variant and the potential causative mutation should be further considered. Whether variants in OR2W3 have any bearing on the development of RP remains undetermined. 
References
Ma X, Guan L, Wu W, et al. Whole-exome sequencing identifies OR2W3 mutation as a cause of autosomal dominant retinitis pigmentosa. Sci Rep. 2015; 5: 9236.
Hu DN. Genetic aspects of retinitis pigmentosa in China. Am J Med Genet. 1982; 12: 51–56.
Boughman JA, Conneally PM, Nance WE. Population genetic studies of retinitis pigmentosa. Am J Hum Genet. 1980; 32: 223–235.
1000 Genomes Project Consortium Abecasis GR, Auton A, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012; 491: 56–65.
Exome Aggregation Consortium (ExAC), Cambridge, MA. Available at: http://exac.broadinstitute.org. Accessed August 20, 2015.
Liu X, Jian X. Boerwinkle E. dbNSFP v2.0: a database of human non-synonymous SNVs and their functional predictions and annotations. Hum Mutat. 2013; 34: E2393 –E2402.
Figure
 
Protein sequence alignment of seven OR2W3 orthologs shows that the region with the variant (p.R142W) is not conserved.
Figure
 
Protein sequence alignment of seven OR2W3 orthologs shows that the region with the variant (p.R142W) is not conserved.
Table
 
Functional Prediction of c.C424T/p.R142W in OR2W3
Table
 
Functional Prediction of c.C424T/p.R142W in OR2W3
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