title: Homozygous loss-of-function mutation of the LEPREL1 gene causes severe non-syndromic high myopia with early-onset cataract.
abstract: High myopia is a severe visual impairment which can increase the risk of retinal degeneration, subretinal hemorrhage, choroidal neovascularization, cataract and retinal detachment. We recruited an autosomal-recessive high myopia family, with affected subjects who also present early-onset cataract, retinal degeneration and other complications. Using targeted capturing and whole exome sequencing, we identified a homozygous non-sense mutation in the LEPREL1 gene which causes premature termination of the translation at the fifth amino acid (c.13C>T; p.Q5X), co-segregating with the phenotypes. LEPREL1 encodes a proline hydroxylase called prolyl 3-hydroxylase 2 (P3H2), a 2-oxoglutarate-dependent dioxygenase that hydroxylates collagens. The results show that LEPREL1 plays an important role in eye development and homozygous loss-of-function mutation of this gene can cause severely high myopia and early-onset cataract. Our study also strongly suggests that the disruption of collagen modification is one of the pathogenic mechanisms of high myopia and cataract.
authors.affiliation: State Key Laboratory of Medical Genetics, Changsha, Hunan, China.
authors.forename: H
authors.initials: H
authors.lastname: Guo
authors.forename: P
authors.initials: P
authors.lastname: Tong
authors.forename: Y
authors.initials: Y
authors.lastname: Peng
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: Q
authors.initials: Q
authors.lastname: Tian
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.forename: L
authors.initials: L
authors.lastname: Xiao
authors.forename: W
authors.initials: W
authors.lastname: Xiong
authors.forename: Q
authors.initials: Q
authors.lastname: Pan
authors.forename: Z
authors.initials: Z
authors.lastname: Hu
authors.forename: K
authors.initials: K
authors.lastname: Xia
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D044466:Asian People / Q000235:genetics; D002386:Cataract / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D018389:Codon, Nonsense; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009216:Myopia / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D011393:Procollagen-Proline Dioxygenase; C568061:P3H2 protein, human
keywords: LEPREL1; cataract; exome sequencing; high myopia