title: Exome sequencing identifies RDH12 compound heterozygous mutations in a family with severe retinitis pigmentosa.
abstract: OBJECTIVE
  Retinitis 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  No 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Department of Genetics-Research Unit, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.
authors.forename: Oscar F
authors.initials: OF
authors.lastname: Chacon-Camacho
authors.forename: Serguei
authors.initials: S
authors.lastname: Jitskii
authors.forename: Beatriz
authors.initials: B
authors.lastname: Buentello-Volante
authors.forename: Jonathan
authors.initials: J
authors.lastname: Quevedo-Martinez
authors.forename: Juan C
authors.initials: JC
authors.lastname: Zenteno
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D005808:Genes, Recessive; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology
chemical_list: D000429:Alcohol Oxidoreductases; C489649:RDH12 protein, human
keywords: A; BRLMM; Bayesian robust linear model with Mahalanobis distance classifier; Bp; C; Compound heterozygosity; DNA; ERG; Exome sequencing; FAG; GCOS; GeneChip Operating Software; I; L; LCA; LM-PCR; Leber congenital amaurosis; Logmar; MgCl2; NAD(P); Ng; OCT; P; PCR; PolyPhen2; RDH12; RP; Retinal dystrophy; Retinitis pigmentosa; SIFT; SNP; T; adenine; arRP; autosomal recessive retinitis pigmentosa; base pairs; cytosine; desoxirribonucleic acid; electroretinogram; fluorescein retinal angiography; isoleucine; leucine; ligation mediated-PCR; logarithm of the minimum angle of resolution; magnesium chloride; microliter; nanogram; nicotinamide adenine dinucleotide phosphate; optical coherence tomography; polymerase chain reaction; polymorphism phenotyping 2; proline; retinitis pigmentosa; retinol dehydrogenase 12; single nucleotide polymorphism; sorting intolerant from tolerant; thymine; μl