Recessive Mutations in LEPREL1 Underlie a Recognizable Lens Subluxation Phenotype. (March 2015)

• Record Type: Journal Article
• Authors: Khan, Arif O.; Aldahmesh, Mohammed A.; Alsharif, Hadeel; Alkuraya, Fowzan S.
• Is Part Of: Ophthalmic genetics. Volume 36:Number 1(2015:Mar.)
• Page Start: 58
• Page End: 63
• Publication Date: 2015-03
• Subjects: Eye -- Diseases -- Genetic aspects -- Periodicals; Eye Diseases -- genetics -- Periodicals; Eye Diseases -- in infancy & childhood -- Periodicals; 617.7
• DOI: 10.3109/13816810.2014.985847
• Languages: English
• ISSNs: 1381-6810

Abstract

<abstract> <title>Abstract</title> <p> <italic>Purpose</italic>: To uncover the homozygous recessive gene mutation underlying familial lens subluxation and/or juvenile lens opacities in four sisters from a consanguineous family.</p> <p> <italic>Methods</italic>: Prospective family study (clinical phenotyping; homozygosity-analysis-guided candidate gene testing).</p> <p> <italic>Results</italic>: 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 <italic>LEPREL1</italic> (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.</p> <p> <italic>Conclusions</italic>: Recessive <italic>LEPREL1</italic> 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.</p> </abstract>