title: Mutations in RD3 are associated with an extremely rare and severe form of early onset retinal dystrophy.
abstract: OBJECTIVE
  To identify the underlying mutation and describe the phenotype in a consanguineous Kurdish family with Leber's congenital amaurosis (LCA)/early onset severe retinal dystrophy (EOSRD).
  
  
  METHODS
  Members of the index family were followed up to 22 years by ophthalmological examinations, including best corrected visual acuity (BCVA), Goldmann visual field (GVF), two-color-threshold perimetry (2CTP) and Ganzfeld electroretinogram (ERG), fundus photographs, fundus autofluorescence (FAF), and optical coherence tomography (OCT). After excluding seven of nine known LCA/EOSRD genes in the index patient, linkage analysis was performed in the family using a microarray followed by microsatellite fine mapping and direct sequencing of candidate genes. RD3 was screened by direct sequencing of 85 independent patients with LCA/EOSRD presenting with a BCVA ≥ 1.0 LogMAR before the age of 2 years to assess the prevalence of RD3 mutations in LCA/EOSRD. Since RD3 and RetGC1 have a functional relation, study authors screened for a modifying effect of RD3 mutations in 17 independent patients with mutations in GUCY2D.
  
  
  RESULTS
  BCVA was severely reduced from the earliest examinations (as early as 3 months), never exceeding 1.3 LogMAR. The disease presented as cone-rod dystrophy with dystrophic changes in the macula and bone spicules in the periphery on progression. Linkage analysis narrowed the region of interest towards the LCA12 locus. Direct sequencing of RD3 revealed a homozygous nonsense mutation (c.180C > A) in all affected members tested. Screening of additional unrelated LCA/EOSRD patients revealed only polymorphisms in RD3.
  
  
  CONCLUSIONS
  This is the second family reported so far with mutations in RD3. Mutations in RD3 are a very rare cause of LCA associated with an extremely severe form of retinal dystrophy.
authors.affiliation: Department of Ophthalmology, Laboratory of Molecular Ophthalmology, Justus-Liebig-University, Germany. markus.preising@uniklinikum-giessen.de
authors.forename: Markus N
authors.initials: MN
authors.lastname: Preising
authors.forename: Nora
authors.initials: N
authors.lastname: Hausotter-Will
authors.forename: Manuel C
authors.initials: MC
authors.lastname: Solbach
authors.forename: Christoph
authors.initials: C
authors.lastname: Friedburg
authors.forename: Franz
authors.initials: F
authors.lastname: Rüschendorf
authors.forename: Birgit
authors.initials: B
authors.lastname: Lorenz
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D003241:Consanguinity; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D057130:Leber Congenital Amaurosis / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D058499:Retinal Dystrophies / Q000235:genetics* / Q000503:physiopathology; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D005136:Eye Proteins; C477438:RD3 protein, human