title: Variations in NPHP5 in patients with nonsyndromic leber congenital amaurosis and Senior-Loken syndrome.
abstract: OBJECTIVE
  To investigate whether mutations in NPHP5 can cause Leber congenital amaurosis (LCA) without early-onset renal disease.
  
  
  METHODS
  DNA samples from 276 individuals with nonsyndromic LCA were screened for variations in the NPHP5 gene. Each had been previously screened for mutations in 8 known LCA genes without identifying a disease-causing genotype.
  
  
  RESULTS
  Nine of the 276 LCA probands (3.2%) harbored 2 plausible disease-causing mutations (7 different alleles) in NPHP5. Four of these have been previously reported in patients with Senior-Loken syndrome (F141del, R461X, H506del, and R489X) and 3 are novel (A111del, E346X, and R455X). All 9 patients had severe visual loss from early childhood but none had overt renal disease in the first decade of life. Two patients were diagnosed with nephronophthisis in the second decade. Retinal imaging studies showed retained photoreceptor nuclei and retinal pigment epithelium integrity mainly in the cone-rich central retina, a phenotype with strong similarities to that of NPHP6 disease.
  
  
  CONCLUSIONS
  Mutations in NPHP5 can cause LCA without early-onset renal disease. Abnormalities observed in the photoreceptor outer segments (a cilial structure) may explain the severe visual loss in NPHP5 -associated LCA. Clinical Relevance  The persistence of central photoreceptor nuclei despite severe visual loss in NPHP5 disease is encouraging for future therapeutic interventions.
authors.affiliation: Department of Ophthalmology and Visual Sciences, The University of Iowa, 375 Newton Rd, 4111 MERF, Iowa City, IA 52242, USA. edwin-stone@uiowa.edu
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Artur V
authors.initials: AV
authors.lastname: Cideciyan
authors.forename: Tomas S
authors.initials: TS
authors.lastname: Aleman
authors.forename: Todd E
authors.initials: TE
authors.lastname: Scheetz
authors.forename: Alexander
authors.initials: A
authors.lastname: Sumaroka
authors.forename: Mary A
authors.initials: MA
authors.lastname: Ehlinger
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Schwartz
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Fishman
authors.forename: Elias I
authors.initials: EI
authors.lastname: Traboulsi
authors.forename: Byron L
authors.initials: BL
authors.lastname: Lam
authors.forename: Anne B
authors.initials: AB
authors.lastname: Fulton
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
mesh_terms: D000293:Adolescent; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D000072661:Ciliopathies; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D052177:Kidney Diseases, Cystic / Q000175:diagnosis / Q000235:genetics; D057130:Leber Congenital Amaurosis / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D009887:Ophthalmoscopy; D015418:Optic Atrophies, Hereditary / Q000175:diagnosis / Q000235:genetics; D010375:Pedigree; D012160:Retina / Q000473:pathology; D041623:Tomography, Optical Coherence; D014786:Vision Disorders / Q000175:diagnosis / Q000235:genetics; D055815:Young Adult
chemical_list: D002148:Calmodulin-Binding Proteins; C498171:IQCB1 protein, human