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Identification and functional analysis of a novel oculocerebrorenal syndrome of Lowe (OCRL) gene variant in two pedigrees with varying phenotypes including isolated congenital cataract

PURPOSE: To identify the genetic variation in two unrelated probands with congenital cataract and to perform functional analysis of the detected variants. METHODS: Clinical examination and phenotyping, segregation, and functional analysis were performed for the two studied pedigrees. RESULTS: A nove...

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Autores principales: Shalaby, Ahmed K., Emery-Billcliff, Peter, Baralle, Diana, Dabir, Tabib, Begum, Shahiba, Waller, Sarah, Tabernero, Lydia, Lowe, Martin, Self, James
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334980/
https://www.ncbi.nlm.nih.gov/pubmed/30713423
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author Shalaby, Ahmed K.
Emery-Billcliff, Peter
Baralle, Diana
Dabir, Tabib
Begum, Shahiba
Waller, Sarah
Tabernero, Lydia
Lowe, Martin
Self, James
author_facet Shalaby, Ahmed K.
Emery-Billcliff, Peter
Baralle, Diana
Dabir, Tabib
Begum, Shahiba
Waller, Sarah
Tabernero, Lydia
Lowe, Martin
Self, James
author_sort Shalaby, Ahmed K.
collection PubMed
description PURPOSE: To identify the genetic variation in two unrelated probands with congenital cataract and to perform functional analysis of the detected variants. METHODS: Clinical examination and phenotyping, segregation, and functional analysis were performed for the two studied pedigrees. RESULTS: A novel OCRL gene variant (c.1964A>T, p. (Asp655Val)) was identified. This variant causes defects in OCRL protein folding and mislocalization to the cytoplasm. In addition, the variant’s location close to the Rab binding site is likely to be associated with membrane targeting abnormalities. CONCLUSIONS: The results highlight the importance of early genetic diagnosis in infants with congenital cataract and show that mutations in the OCRL gene can present as apparently isolated congenital cataract.
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spelling pubmed-63349802019-02-01 Identification and functional analysis of a novel oculocerebrorenal syndrome of Lowe (OCRL) gene variant in two pedigrees with varying phenotypes including isolated congenital cataract Shalaby, Ahmed K. Emery-Billcliff, Peter Baralle, Diana Dabir, Tabib Begum, Shahiba Waller, Sarah Tabernero, Lydia Lowe, Martin Self, James Mol Vis Research Article PURPOSE: To identify the genetic variation in two unrelated probands with congenital cataract and to perform functional analysis of the detected variants. METHODS: Clinical examination and phenotyping, segregation, and functional analysis were performed for the two studied pedigrees. RESULTS: A novel OCRL gene variant (c.1964A>T, p. (Asp655Val)) was identified. This variant causes defects in OCRL protein folding and mislocalization to the cytoplasm. In addition, the variant’s location close to the Rab binding site is likely to be associated with membrane targeting abnormalities. CONCLUSIONS: The results highlight the importance of early genetic diagnosis in infants with congenital cataract and show that mutations in the OCRL gene can present as apparently isolated congenital cataract. Molecular Vision 2018-12-31 /pmc/articles/PMC6334980/ /pubmed/30713423 Text en Copyright © 2018 Molecular Vision. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed.
spellingShingle Research Article
Shalaby, Ahmed K.
Emery-Billcliff, Peter
Baralle, Diana
Dabir, Tabib
Begum, Shahiba
Waller, Sarah
Tabernero, Lydia
Lowe, Martin
Self, James
Identification and functional analysis of a novel oculocerebrorenal syndrome of Lowe (OCRL) gene variant in two pedigrees with varying phenotypes including isolated congenital cataract
title Identification and functional analysis of a novel oculocerebrorenal syndrome of Lowe (OCRL) gene variant in two pedigrees with varying phenotypes including isolated congenital cataract
title_full Identification and functional analysis of a novel oculocerebrorenal syndrome of Lowe (OCRL) gene variant in two pedigrees with varying phenotypes including isolated congenital cataract
title_fullStr Identification and functional analysis of a novel oculocerebrorenal syndrome of Lowe (OCRL) gene variant in two pedigrees with varying phenotypes including isolated congenital cataract
title_full_unstemmed Identification and functional analysis of a novel oculocerebrorenal syndrome of Lowe (OCRL) gene variant in two pedigrees with varying phenotypes including isolated congenital cataract
title_short Identification and functional analysis of a novel oculocerebrorenal syndrome of Lowe (OCRL) gene variant in two pedigrees with varying phenotypes including isolated congenital cataract
title_sort identification and functional analysis of a novel oculocerebrorenal syndrome of lowe (ocrl) gene variant in two pedigrees with varying phenotypes including isolated congenital cataract
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334980/
https://www.ncbi.nlm.nih.gov/pubmed/30713423
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