title: RDH12 retinopathy: novel mutations and phenotypic description.
abstract: OBJECTIVE
  To identify patients with autosomal recessive retinal dystrophy caused by mutations in the gene, retinal dehydrogenase 12 (RDH12), and to report the associated phenotype.
  
  
  METHODS
  After giving informed consent, all patients underwent full clinical evaluation. Patients were selected for mutation analysis based upon positive results from the Asper Ophthalmics Leber congenital amaurosis arrayed primer extansion (APEX) microarray screening, linkage analysis, or their clinical phenotype. All coding exons of RDH12 were screened by direct Sanger sequencing. Potential variants were checked for segregation in the respective families and screened in controls, and their pathogenicity analyzed using in silico prediction programs.
  
  
  RESULTS
  Screening of 389 probands by the APEX microarray and/or direct sequencing identified bi-allelic mutations in 29 families. Seventeen novel mutations were identified. The phenotype in these patients presented with a severe early-onset rod-cone dystrophy. Funduscopy showed severe generalized retinal pigment epithelial and retinal atrophy, which progressed to dense, widespread intraretinal pigment migration by adulthood. The macula showed severe atrophy, with pigmentation and yellowing, and corresponding loss of fundus autofluorescence. Optical coherence tomography revealed marked retinal thinning and excavation at the macula.
  
  
  CONCLUSIONS
  RDH12 mutations account for approximately 7% of disease in our cohort of patients diagnosed with Leber congenital amaurosis and early-onset retinal dystrophy. The clinical features of this disorder are highly characteristic and facilitate candidate gene screening. The term RDH12 retinopathy is proposed as a more accurate description.
authors: Department of Genetics, Institute of Ophthalmology, London, UK. d.mackay@ucl.ac.uk
authors: Donna S
authors: DS
authors: Mackay
authors: Arundhati
authors: A
authors: Dev Borman
authors: Phillip
authors: P
authors: Moradi
authors: Robert H
authors: RH
authors: Henderson
authors: Zheng
authors: Z
authors: Li
authors: Genevieve A
authors: GA
authors: Wright
authors: Naushin
authors: N
authors: Waseem
authors: Mamatha
authors: M
authors: Gandra
authors: Dorothy A
authors: DA
authors: Thompson
authors: Shomi S
authors: SS
authors: Bhattacharya
authors: Graham E
authors: GE
authors: Holder
authors: Andrew R
authors: AR
authors: Webster
authors: Anthony T
authors: AT
authors: Moore
mesh_terms: D017668:Age of Onset; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007223:Infant; D057130:Leber Congenital Amaurosis / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D006113:United Kingdom
chemical_list: D005136:Eye Proteins; D000429:Alcohol Oxidoreductases; C489649:RDH12 protein, human