Abstract
Retinitis punctata albescens (RPA) is an ocular disease characterized by decreased visual acuity, night blindness, atropic maculopathy, and pigmentary retinopathy. Multiple genes have been linked to the etiology of RPA. In this study, we investigated the genetic causes of RPA in a consanguineous Pakistani family with multiple affected individuals. We performed whole-exome sequencing of seven family members, and screened variants co-segregating with RPA in recessive fashion. Bioinformatic and in silico analyses revealed that all affected individuals were homozygous for a novel mutation that substitutes glycine with arginine at position 66 (c.196 G>C) in exon 2 of the lecithin retinol acyltransferase (LRAT) that converts all-trans retinol to 11-cis retinal in the retinal pigment epithelium. This mutation was not present in 217 unrelated Pakistani control subjects nor in the Exome Aggregation Consortium database containing exome data from 60,638 individuals worldwide. Mutations in the LRAT gene were previously found from the patients with Leber congenital amaurosis and retinal dystrophy, however, we report first time that disruptions in this gene are also associated with RPA.
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Acknowledgments
This study was supported to CK by the Basic Science Research Program of the National Research Foundation of Korea funded by the Ministry of Education (No. 2013R1A1A2061259) and an intramural grant from Sungshin Women’s University (2013-1-11-062/1).
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Written informed consent was obtained from all study participants from this family. This study was approved by the Institutional Review Board Committees at Quaid-i-Azam University (Islamabad, Pakistan) and Sungshin Women’s University (Seoul, South Korea).
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Musharraf Jelani and Miyeon Jeon contributed equally to this work.
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Jelani, M., Jeon, M., Rahman, O.U. et al. Whole-exome sequencing identifies a novel LRAT mutation underlying retinitis punctata albescens in a consanguineous Pakistani family. Genes Genom 37, 845–849 (2015). https://doi.org/10.1007/s13258-015-0311-4
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DOI: https://doi.org/10.1007/s13258-015-0311-4