Progress in clinical research of congenital membranous cataract / 国际眼科杂志(Guoji Yanke Zazhi)

@#Congenital cataract is one of the leading causes of childhood blindness and congenital membranous cataract is a rare and special type of congenital cataract. The lens fibre of congenital membranous cataract is degenerative and its cortex is absorbed gradually. Congenital membranous cataract also has another name, pseudoaphakia, due to the similar phenotype with posterior capsule opacification after cataract surgery, but without intraocular refractive power. There are few reports on congenital membranous cataract at home and abroad, and the research on the pathogenesis of congenital membranous cataract is even less. Clarifying the pathogenesis of congenital membranous cataract, especially the genetics, is very helpful for us to understand the pathogenesis of congenital cataract and the molecular mechanism of lens development.

The novel mutation P36R in LRP5L contributes to congenital membranous cataract via inhibition of laminin γ1 and c-MAF.

PURPOSE: The present study investigated a pathogenic mutation and its mechanism on membranous cataract in a congenital membranous cataract family. METHODS: An autosomal dominant four-generation Chinese congenital membranous cataract family was recruited and whole-exome sequencing was performed to screen for sequence variants. Candidate variants were validated using polymerase chain reaction and Sanger sequencing. Wild-type and mutant low-density lipoprotein receptor-related protein 5-like (LRP5L) plasmids were constructed and transfected into human lens epithelial cells (HLE B-3) and human anterior lens capsules. The cell lysates, nuclear and cytoplasmic proteins, and basement membrane components of HLE B-3 cells were harvested. LRP5L and laminin γ1 were knocked down in HLE B-3 cells using specific small-interfering RNA. The protein expression levels of LRP5L, laminin γ1, and c-MAF were detected using immunoblotting and immunofluorescence. RESULTS: We identified a novel suspected pathogenic mutation in LRP5L (c.107C > G, p.P36R) in the congenital membranous cataract family. This mutation was absent in 300 normal controls and 300 age-related cataract patients. Bioinformatics analysis with PolyPhen-2 and SIFT suggested that LRP5L-P36R was pathogenic. LRP5L upregulated laminin γ1 expression in the cytoplasmic proteins of HLE B-3 cells and human anterior lens capsules, and LRP5L-P36R inhibited the effects of LRP5L. LRP5L upregulated c-MAF expression in the nucleus and cytoplasm of HLE B-3 cells, and LRP5L-P36R inhibited c-MAF expression via inhibition of laminin γ1. CONCLUSION: Our study identified a novel gene, LRP5L, associated with congenital membranous cataract, and its mutant LRP5L-P36R contributed to membranous cataract development via inhibition of laminin γ1 and c-MAF.

Novel mutation in OCRL leading to a severe form of Lowe syndrome.

AIM: To investigate the phenotype and genotype of a family with X-linked recessive Lowe syndrome. METHODS: All the members in the Chinese pedigree underwent comprehensive ophthalmologic and systemic examinations. Genomic DNA was isolated from peripheral blood of the pedigree members and 100 unrelated healthy Chinese subjects. Direct sequencing was performed to screen the exons and intron boundaries of OCRL. RESULTS: The ophthalmological and systemic examinations suggested that the affected individual had Lowe syndrome. The phenotype in the pedigree is severe and consistent among all the affected individuals except for an individual who additionally suffered from congenital heart disease and laryngeal cartilage dysplasia. Directional Sanger sequencing identified a complex mutation c.(2368_2368delG; c.2370A>C) in the Rho-GTPase activating protein domain. This complex mutation causes termination of protein synthesis at amino acid 824 and result in a new peptide with 823 amino acids (p.Ala790ProfsX34). This mutation was not detected in 100 unrelated healthy Chinese subjects. CONCLUSION: Our findings expand the phenotypic and genotypic spectrum of Lowe syndrome.

Congenital membranous cataract associated with persistent fetal vasculature.

A 15-year-old boy underwent phacoemulsification for a membranous cataract during which the presence of anterior persistent hyaloid artery and elongated ciliary processes were discovered. A posterior capsulorhexis was performed and the anterior part of the persistent hyaloid artery stalk was resected together with the posterior capsule. A foldable intraocular lens was implanted and the optic was captured in the posterior capsulorhexis margin. This is an unusual case of congenital membranous cataract associated with malformations of persistent fetal vasculature and elongated ciliary processes.