title: Clinical features of a novel TIMP-3 mutation causing Sorsby's fundus dystrophy: implications for disease mechanism.
abstract: OBJECTIVE
  To describe the phenotype in three family members affected by a novel mutation in the gene coding for the enzyme tissue inhibitor of metalloproteinase-3 (TIMP-3).
  
  
  METHODS
  Three members of the same family were seen with a history of nyctalopia and visual loss due to maculopathy. Clinical features were consistent with Sorsby's fundus dystrophy. Exon 5 of the gene coding for TIMP-3 was amplified by the polymerase chain reaction, single strand conformation polymorphism analysis undertaken and exon 5 amplicons were directly sequenced.
  
  
  RESULTS
  Onset of symptoms was in the third to fourth decade. Five of six eyes had geographic macular atrophy rather than neovascularisation as a cause for central visual loss. Peripheral retinal pigmentary disturbances were present. Scotopic ERGs were abnormal in all three. Mutation analysis showed a G-->T transversion in all three resulting in a premature termination codon, E139X, deleting most of the carboxy terminal domain of TIMP-3.
  
  
  CONCLUSIONS
  The patients described had a form of Sorsby's fundus dystrophy which fell at the severe end of the spectrum of this disease. Postulated disease mechanisms include deposition of dimerised TIMP-3 protein.
authors.affiliation: Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne NE2 4HH, UK. M.P.Clarke@ncl.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Clarke
authors.forename: K W
authors.initials: KW
authors.lastname: Mitchell
authors.forename: J
authors.initials: J
authors.lastname: Goodship
authors.forename: S
authors.initials: S
authors.lastname: McDonnell
authors.forename: M D
authors.initials: MD
authors.lastname: Barker
authors.forename: I D
authors.initials: ID
authors.lastname: Griffiths
authors.forename: N
authors.initials: N
authors.lastname: McKie
mesh_terms: D000328:Adult; D000368:Aged; D018389:Codon, Nonsense; D004596:Electroretinography; D005451:Fluorescein Angiography; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D019717:Tissue Inhibitor of Metalloproteinase-3