title: Tubby-like protein 1 homozygous splice-site mutation causes early-onset severe retinal degeneration.
abstract: OBJECTIVE
  To characterize the disease expression of an autosomal recessive human retinal degeneration associated with a mutation in TULP1 (tubby-like protein 1), a gene with currently unknown function.
  
  
  METHODS
  Homozygotes and heterozygotes from an extended Dominican kindred with a TULP1 splice-site gene mutation (IVS14+1,G-->A) were studied clinically and with visual function tests. Sequence analysis of TULP1 was also performed in unrelated patients with severe retinal degeneration from a North American clinic population.
  
  
  RESULTS
  Homozygotes had nystagmus, visual acuity of 20/200 or worse, color vision disturbances, bull's eye maculopathy, and peripheral pigmentary retinopathy. Younger patients had a relatively wide extent of kinetic visual fields; older patients had only peripheral islands. No rod function was measurable by psychophysics in any of the patients; markedly reduced cone function was detectable across the visual field of younger patients and in the remaining peripheral islands of older patients. Rod and cone electroretinograms (ERGs) were not detectable using standard methods; microvolt-level cone ERGs were present in some patients. Heterozygotes had normal visual function. No putative pathogenic sequence changes in TULP1 were observed in North American patients with comparably severe retinal phenotypes, mainly in the diagnostic category of Leber congenital amaurosis.
  
  
  CONCLUSIONS
  This TULP1 splice-site mutation in homozygotes causes early-onset, severe retinal degeneration involving macular and peripheral cones and rods. The constellation of phenotypic findings suggests that the TULP1 gene product is critically important for normal photoreceptor function and may play a role in retinal development.
authors.affiliation: Riverview Medical Center, Carrabelle, Florida, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Lewis
authors.forename: I R
authors.initials: IR
authors.lastname: Batlle
authors.forename: K G
authors.initials: KG
authors.lastname: Batlle
authors.forename: P
authors.initials: P
authors.lastname: Banerjee
authors.forename: A V
authors.initials: AV
authors.lastname: Cideciyan
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: T S
authors.initials: TS
authors.lastname: Alemán
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Ott
authors.forename: T C
authors.initials: TC
authors.lastname: Gilliam
authors.forename: J A
authors.initials: JA
authors.lastname: Knowles
authors.forename: S G
authors.initials: SG
authors.lastname: Jacobson
mesh_terms: D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing / Q000235:genetics*; D002648:Child; D003117:Color Vision Defects / Q000235:genetics / Q000503:physiopathology; D004247:DNA / Q000032:analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005654:Fundus Oculi; D006801:Humans; D008297:Male; D009759:Nystagmus, Pathologic / Q000235:genetics / Q000503:physiopathology; D010375:Pedigree; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology; D014792:Visual Acuity; D014794:Visual Fields
chemical_list: D005136:Eye Proteins; C105443:TULP1 protein, human; D004247:DNA