title: Expansion of ocular phenotypic features associated with mutations in ADAMTS18.
abstract: OBJECTIVE
  We describe novel ocular phenotypic features caused by mutations in ADAMTS18. The exact role of ADAMTS18 in ocular disease is unclear, and our work further contributes to the understanding of this gene and its protein.
  
  
  OBJECTIVE
  To expand the phenotypic characterization in patients with homozygous mutations in ADAMTS18 and report novel mutational data.
  
  
  METHODS
  A case series with genetic investigations was conducted at tertiary referral clinical and university settings. Three families participated.
  
  
  METHODS
  Phenotype and genotype description of 3 families.
  
  
  RESULTS
  Four affected patients from 3 families with an unusual ocular phenotype had full ophthalmic and systemic examination. A single affected individual in the first family had bilateral microcornea, ectopic pupils, and cone-rod dystrophy. In a second family, 2 brothers showed bilateral microcornea, childhood cataract, ectopia lentis, rhegmatogenous retinal detachment, and cone-rod dystrophy. In the third family, a single affected individual had the same features as those in family 2, without ectopia lentis. Causative mutations were sought using homozygosity mapping, Sanger sequencing, and massively parallel sequencing of the whole exome. Novel homozygous mutations in ADAMTS18 were identified, consisting of c.1067T>A [p.L356*] in the first proband, c.2159G>C [p.C720S] in the 2 affected brothers, and c.1952G>A [p.R651Q] in the third proband. All 3 mutations are predicted to be pathogenic.
  
  
  CONCLUSIONS
  Mutations in ADAMTS18 are associated with ocular developmental abnormalities including microcornea, ectopia lentis, and early onset of cone-rod dystrophy. This report provides further evidence that ADAMTS18 plays a key role in ocular development. Physicians should consider screening ADAMTS18 in patients with microcornea and cone-rod dystrophy.
authors.affiliation: University College London Institute of Ophthalmology, London, England2Vitreoretinal Department, Moorfields Eye Hospital, London, England3Professorial Unit, Moorfields Eye Hospital, London, England.
authors.forename: Aman
authors.initials: A
authors.lastname: Chandra
authors.affiliation: University College London Institute of Ophthalmology, London, England.
authors.forename: Gavin
authors.initials: G
authors.lastname: Arno
authors.affiliation: Medical Research Council Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh, Scotland.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Williamson
authors.affiliation: University College London Institute of Ophthalmology, London, England3Professorial Unit, Moorfields Eye Hospital, London, England.
authors.forename: Panagiotis I
authors.initials: PI
authors.lastname: Sergouniotis
authors.affiliation: Department of Ophthalmology, Justus-Liebig University, Giessen, Germany.
authors.forename: Markus N
authors.initials: MN
authors.lastname: Preising
authors.affiliation: Vitreoretinal Department, Moorfields Eye Hospital, London, England.
authors.forename: David G
authors.initials: DG
authors.lastname: Charteris
authors.affiliation: Clinical and Academic Department of Ophthalmology, Great Ormond Street Hospital for Children, London, England.
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Thompson
authors.affiliation: University College London Institute of Ophthalmology, London, England7Electrodiagnostics, Moorfields Eye Hospital, London, England.
authors.forename: Graham E
authors.initials: GE
authors.lastname: Holder
authors.affiliation: University College London Institute of Ophthalmology, London, England3Professorial Unit, Moorfields Eye Hospital, London, England.
authors.forename: Arundhati Dev
authors.initials: AD
authors.lastname: Borman
authors.affiliation: Radiology, Moorfields Eye Hospital, London, England.
authors.forename: Indran
authors.initials: I
authors.lastname: Davagnanam
authors.affiliation: University College London Institute of Ophthalmology, London, England3Professorial Unit, Moorfields Eye Hospital, London, England.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
authors.affiliation: Department of Ophthalmology, Justus-Liebig University, Giessen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Lorenz
authors.affiliation: Medical Research Council Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh, Scotland.
authors.forename: David R
authors.initials: DR
authors.lastname: FitzPatrick
authors.affiliation: University College London Institute of Ophthalmology, London, England3Professorial Unit, Moorfields Eye Hospital, London, England6Clinical and Academic Department of Ophthalmology, Great Ormond Street Hospital for Children, London, England.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000071096:ADAMTS Proteins; D000293:Adolescent; D000328:Adult; D005124:Eye Abnormalities / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype
chemical_list: D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C510099:ADAMTS18 protein, human