Recessive Mutations in LEPREL1 Underlie a Recognizable Lens Subluxation Phenotype

Abstract

Purpose: 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.

• Ectopia lentis
• lens subluxation
• LEPREL1

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This study received financial support from King Abdulaziz City for Science and Technology to FSA [Grant 10-BIO 1350-20]. The funding organization had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.