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Graefe's Archive for Clinical and Experimental Ophthalmology

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13.08.2020 | Cataract

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

verfasst von: Liyao Sun, Fanqian Song, Hanruo Liu, Chao Wang, Xianling Tang, Zhijian Li, Hongyan Ge, Ping Liu

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 12/2020

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Abstract

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.

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Titel: The novel mutation P36R in LRP5L contributes to congenital membranous cataract via inhibition of laminin γ1 and c-MAF
verfasst von: Liyao Sun
Fanqian Song
Hanruo Liu
Chao Wang
Xianling Tang
Zhijian Li
Hongyan Ge
Ping Liu
Publikationsdatum: 13.08.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 12/2020
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-020-04846-x

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

Abstract

Purpose

Methods

Results

Conclusion

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

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