title: Homozygous mutation in MERTK causes severe autosomal recessive retinitis pigmentosa.
abstract: OBJECTIVE
  Gene identification in retinitis pigmentosa is a prerequisite to future therapies. Accordingly, autosomal recessive retinitis pigmentosa families were genotyped to search for causative mutations.
  
  
  METHODS
  Members of a consanguineous Moroccan family had standard ophthalmologic examination, optical coherence tomography-3 scan, autofluorescence testing, and electroretinogram. Their DNA was genotyped with the 250K SNP microchip (Affymetrix) and homozygosity mapping was done. MERTK exons were polymerase chain reaction amplified and sequenced.
  
  
  RESULTS
  Two sisters and one brother out of 6 siblings had rod cone dystrophy type of retinitis pigmentosa. Salient features were night blindness starting in early infancy, dot-like whitish deposits in fovea and macula with corresponding autofluorescent dots in youngest patients, decreased visual acuity, and cone responses higher than rod responses at electroretinogram. The patients were homozygous in regions from chromosomes 2 and 8, but only that of chromosome 2 was inherited from a common ancestor. Sequencing of the MERTK gene belonging to the chromosome 2 region showed that the 3 affected patients carried a novel homozygous mutation in exon 17, c.2323C>T, leading to p.Arg775X, while their unaffected brothers and sister, parents, and paternal grandfather were heterozygous.
  
  
  CONCLUSIONS
  MERTK mutations lead to severe retinitis pigmentosa with discrete dot-like autofluorescent deposits at early stages, which are a hallmark of this MERTK-specific dystrophy.
authors.affiliation: INSERM 1051, Institute for Neurosciences of Montpellier, Montpellier, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ksantini
authors.forename: Estèle
authors.initials: E
authors.lastname: Lafont
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bocquet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meunier
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
mesh_terms: D000293:Adolescent; D002648:Child; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D005808:Genes, Recessive; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D035781:Siblings; D041623:Tomography, Optical Coherence; D000076202:c-Mer Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; C097072:MERTK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase