Exome sequencing identifies RDH12 compound heterozygous mutations in a family with severe retinitis pigmentosa |
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Authors: | Oscar F. Chacon-Camacho Serguei Jitskii Beatriz Buentello-Volante Jonathan Quevedo-Martinez Juan C. Zenteno |
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Affiliation: | 1. Department of Genetics-Research Unit, Institute of Ophthalmology “Conde de Valenciana”, Mexico City, Mexico;2. Retinal Pathology Treatment Center “Mexico with Vision” Fund, Nezahualcoyotl, México;3. Department of Biochemistry, Faculty of Medicine, UNAM, Mexico City, Mexico |
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Abstract: | ObjectiveRetinitis pigmentosa (RP) is the most prevalent type of inherited retinal degeneration and one of the commonest causes of genetically determined visual dysfunction worldwide. To date, approximately 35 genes have been associated with nonsyndromic autosomal recessive RP (arRP), however the small contribution of each gene to the total prevalence of arRP and the lack of a clear genotype–phenotype correlation complicate the genetic analysis in affected patients. Next generation sequencing technologies are powerful and cost-effective methods for detecting causative mutations in both sporadic and familial RP cases.MethodsA Mexican family with 5 members affected from arRP was studied. All patients underwent a complete ophthalmologic examination. Molecular methods included genome-wide SNP homozygosity mapping, exome sequencing analysis, and Sanger-sequencing confirmation of causal mutations.ResultsNo regions of shared homozygosity among affected subjects were identified. Exome sequencing in a single patient allowed the detection of two missense mutations in the RDH12 gene: a c.446T>C transition predicting a novel p.L149P substitution, and a c.295C>A transversion predicting a previously reported p.L99I replacement. Sanger sequencing confirmed that all affected subjects carried both RDH12 mutations.ConclusionsThis study adds to the molecular spectrum of RDH12-related retinopathy and offers an additional example of the power of exome sequencing in the diagnosis of recessively inherited retinal degenerations. |
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Keywords: | A, adenine arRP, autosomal recessive retinitis pigmentosa Bp, base pairs BRLMM, Bayesian robust linear model with Mahalanobis distance classifier C, cytosine DNA, desoxirribonucleic acid ERG, electroretinogram FAG, fluorescein retinal angiography GCOS, GeneChip Operating Software I, isoleucine L, leucine LCA, Leber congenital amaurosis LM-PCR, ligation mediated-PCR Logmar, logarithm of the minimum angle of resolution MgCl2, magnesium chloride NAD(P), nicotinamide adenine dinucleotide phosphate Ng, nanogram OCT, optical coherence tomography P, proline PCR, polymerase chain reaction PolyPhen2, polymorphism phenotyping 2 RDH12, retinol dehydrogenase 12 RP, retinitis pigmentosa SIFT, sorting intolerant from tolerant SNP, single nucleotide polymorphism T, thymine μl, microliter |
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