title: Recessive mutations in LEPREL1 underlie a recognizable lens subluxation phenotype.
abstract: OBJECTIVE
  To uncover the homozygous recessive gene mutation underlying familial lens subluxation and/or juvenile lens opacities in four sisters from a consanguineous family.
  
  
  METHODS
  Prospective family study (clinical phenotyping; homozygosity-analysis-guided candidate gene testing).
  
  
  RESULTS
  The proband was a 14-year-old girl with long-standing poor vision, bilateral temporal lens subluxation, lens opacities, and axial high myopia. There were no syndromic findings, and fibrillin-1 sequencing was normal. Three sisters, also non-syndromic, had undergone bilateral juvenile lens surgery (two for juvenile cataract, 1 for lens subluxation) within the first two decades of life. Both sisters who had cataract surgery developed bilateral post-operative retinal detachments and one had documented lens instability during cataract surgery. Genetic analysis revealed the phenotype to segregate with a novel homozygous recessive mutation in LEPREL1 (c.292delC; p.Gly100Alafs*104). Recessive mutations in this gene were recently highlighted as a cause for axial myopia and early-onset cataract in two families for whom some affected members also had ectopia lentis and/or post-operative retinal detachments.
  
  
  CONCLUSIONS
  Recessive LEPREL1 mutations should be recognized as part of the differential diagnosis of lens subluxation. The associated phenotype is non-syndromic and distinguishable from other causes of ectopia lentis in the context of its additional features: juvenile lens opacities, axial myopia, and a predisposition to retinal tears/detachment following intraocular surgery.
authors.affiliation: Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital , Riyadh , Saudi Arabia .
authors.forename: Arif O
authors.initials: AO
authors.lastname: Khan
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Aldahmesh
authors.forename: Hadeel
authors.initials: H
authors.lastname: Alsharif
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002386:Cataract / Q000235:genetics; D002387:Cataract Extraction; D002648:Child; D003241:Consanguinity; D004479:Ectopia Lentis / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D005820:Genetic Testing; D006720:Homozygote; D006801:Humans; D007906:Lens Subluxation / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D011393:Procollagen-Proline Dioxygenase; C568061:P3H2 protein, human
keywords: Ectopia lentis; LEPREL1; lens subluxation