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Uveitis and Multiple Sclerosis: Potential Common Causal Mutations

Uveitis, defined as inflammation of the uveal tract of the eye, is a leading cause of blindness and visual impairment throughout the world. The etiology of uveitis is complex, and autoimmunity plays a major role in its pathogenesis. Intermediate uveitis (IU), a subtype of ocular inflammation, has be...

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Autores principales: de-la-Torre, Alejandra, Silva-Aldana, Claudia T., Muñoz-Ortiz, Juliana, Piñeros-Hernández, Laura B., Otero, Oscar, Domínguez, Alejandra, Faciolince, León A., Arcos-Holzinger, Mauricio, Mastronardi, Claudio, Contreras-Bravo, Nora Constanza, Restrepo, Carlos Martín, Arcos-Burgos, Mauricio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834745/
https://www.ncbi.nlm.nih.gov/pubmed/31161422
http://dx.doi.org/10.1007/s12035-019-1630-2
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author de-la-Torre, Alejandra
Silva-Aldana, Claudia T.
Muñoz-Ortiz, Juliana
Piñeros-Hernández, Laura B.
Otero, Oscar
Domínguez, Alejandra
Faciolince, León A.
Arcos-Holzinger, Mauricio
Mastronardi, Claudio
Contreras-Bravo, Nora Constanza
Restrepo, Carlos Martín
Arcos-Burgos, Mauricio
author_facet de-la-Torre, Alejandra
Silva-Aldana, Claudia T.
Muñoz-Ortiz, Juliana
Piñeros-Hernández, Laura B.
Otero, Oscar
Domínguez, Alejandra
Faciolince, León A.
Arcos-Holzinger, Mauricio
Mastronardi, Claudio
Contreras-Bravo, Nora Constanza
Restrepo, Carlos Martín
Arcos-Burgos, Mauricio
author_sort de-la-Torre, Alejandra
collection PubMed
description Uveitis, defined as inflammation of the uveal tract of the eye, is a leading cause of blindness and visual impairment throughout the world. The etiology of uveitis is complex, and autoimmunity plays a major role in its pathogenesis. Intermediate uveitis (IU), a subtype of ocular inflammation, has been associated with systemic autoimmune disorders, specifically with multiple sclerosis (MS). This article reports a rare three-generation family with several members affected by IU (four siblings) and comorbid MS (two siblings fulfilling MS diagnostic criteria and a third sibling presenting some neurological symptoms). Based on the clinical findings, we captured and sequenced whole exomes of seven pedigree members (affected and unaffected). Using a recessive model of transmission with full penetrance, we applied genetic linkage analysis to define minimal critical regions (MCRs) in suggestive or nominal regions of linkage. In these MCRs, we defined functional (some pathogenic), novel, and rare mutations that segregated as homozygous in affected and heterozygous in unaffected family members. The genes harboring these mutations, including DGKI, TNFRSF10A, GNGT1, CPAMD8, and BAFF, which are expressed in both eye and brain tissues and/or are related to autoimmune diseases, provide new avenues to evaluate the inherited causes of these devastating autoimmune conditions.
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spelling pubmed-68347452019-11-20 Uveitis and Multiple Sclerosis: Potential Common Causal Mutations de-la-Torre, Alejandra Silva-Aldana, Claudia T. Muñoz-Ortiz, Juliana Piñeros-Hernández, Laura B. Otero, Oscar Domínguez, Alejandra Faciolince, León A. Arcos-Holzinger, Mauricio Mastronardi, Claudio Contreras-Bravo, Nora Constanza Restrepo, Carlos Martín Arcos-Burgos, Mauricio Mol Neurobiol Article Uveitis, defined as inflammation of the uveal tract of the eye, is a leading cause of blindness and visual impairment throughout the world. The etiology of uveitis is complex, and autoimmunity plays a major role in its pathogenesis. Intermediate uveitis (IU), a subtype of ocular inflammation, has been associated with systemic autoimmune disorders, specifically with multiple sclerosis (MS). This article reports a rare three-generation family with several members affected by IU (four siblings) and comorbid MS (two siblings fulfilling MS diagnostic criteria and a third sibling presenting some neurological symptoms). Based on the clinical findings, we captured and sequenced whole exomes of seven pedigree members (affected and unaffected). Using a recessive model of transmission with full penetrance, we applied genetic linkage analysis to define minimal critical regions (MCRs) in suggestive or nominal regions of linkage. In these MCRs, we defined functional (some pathogenic), novel, and rare mutations that segregated as homozygous in affected and heterozygous in unaffected family members. The genes harboring these mutations, including DGKI, TNFRSF10A, GNGT1, CPAMD8, and BAFF, which are expressed in both eye and brain tissues and/or are related to autoimmune diseases, provide new avenues to evaluate the inherited causes of these devastating autoimmune conditions. Springer US 2019-06-03 2019 /pmc/articles/PMC6834745/ /pubmed/31161422 http://dx.doi.org/10.1007/s12035-019-1630-2 Text en © The Author(s) 2019 https://creativecommons.org/licenses/by/4.0/Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
de-la-Torre, Alejandra
Silva-Aldana, Claudia T.
Muñoz-Ortiz, Juliana
Piñeros-Hernández, Laura B.
Otero, Oscar
Domínguez, Alejandra
Faciolince, León A.
Arcos-Holzinger, Mauricio
Mastronardi, Claudio
Contreras-Bravo, Nora Constanza
Restrepo, Carlos Martín
Arcos-Burgos, Mauricio
Uveitis and Multiple Sclerosis: Potential Common Causal Mutations
title Uveitis and Multiple Sclerosis: Potential Common Causal Mutations
title_full Uveitis and Multiple Sclerosis: Potential Common Causal Mutations
title_fullStr Uveitis and Multiple Sclerosis: Potential Common Causal Mutations
title_full_unstemmed Uveitis and Multiple Sclerosis: Potential Common Causal Mutations
title_short Uveitis and Multiple Sclerosis: Potential Common Causal Mutations
title_sort uveitis and multiple sclerosis: potential common causal mutations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834745/
https://www.ncbi.nlm.nih.gov/pubmed/31161422
http://dx.doi.org/10.1007/s12035-019-1630-2
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