Recessive Mutations in LEPREL1 Underlie a Recognizable Lens Subluxation Phenotype
Recessive Mutations in LEPREL1 Underlie a Recognizable Lens Subluxation Phenotype
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DOI：
10.3109/13816810.2014.985847
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发表时间：
2015-03-01
影响因子：
1.2
通讯作者：
Alkuraya, Fowzan S.
中科院分区：
文献类型：
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作者：
Khan, Arif O.;Aldahmesh, Mohammed A.;Alkuraya, Fowzan S.
目的：揭示纯合隐性基因突变潜在的家族性透镜半脱位和/或青少年透镜混浊在四姐妹篇从一个consangineous family.Methods：前瞻性的家庭研究（临床表型;纯合性分析指导的候选基因testing）。没有综合征的结果，和repeatin-1测序是正常的。三个姐妹篇，也是非综合征，在出生后的前20年内接受了双侧青少年透镜手术（2例青少年白内障，1例透镜半脱位）。两个接受白内障手术的姐妹篇都发生了双侧术后视网膜脱离，其中一个在白内障手术期间记录了透镜不稳定。遗传分析显示，表型与LEPREL 1中的新纯合隐性突变（c.292delC; p.Gly100Alafs*104）分离。在这个基因中的隐性突变最近被强调为轴性近视和早发性白内障在两个家庭中的原因，其中一些受影响的成员也有异位晶状体和/或术后视网膜detretinal.Conclusions：隐性LEPREL 1突变应被确认为透镜半脱位的鉴别诊断的一部分。相关的表型是非综合征的，并且在其附加特征的背景下与晶状体异位的其他原因区分开：青少年透镜混浊、轴性近视和眼内手术后视网膜撕裂/脱离的倾向。
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.