Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783466542191607808 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6834745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT delatorrealejandra uveitisandmultiplesclerosispotentialcommoncausalmutations AT silvaaldanaclaudiat uveitisandmultiplesclerosispotentialcommoncausalmutations AT munozortizjuliana uveitisandmultiplesclerosispotentialcommoncausalmutations AT pineroshernandezlaurab uveitisandmultiplesclerosispotentialcommoncausalmutations AT oterooscar uveitisandmultiplesclerosispotentialcommoncausalmutations AT dominguezalejandra uveitisandmultiplesclerosispotentialcommoncausalmutations AT faciolinceleona uveitisandmultiplesclerosispotentialcommoncausalmutations AT arcosholzingermauricio uveitisandmultiplesclerosispotentialcommoncausalmutations AT mastronardiclaudio uveitisandmultiplesclerosispotentialcommoncausalmutations AT contrerasbravonoraconstanza uveitisandmultiplesclerosispotentialcommoncausalmutations AT restrepocarlosmartin uveitisandmultiplesclerosispotentialcommoncausalmutations AT arcosburgosmauricio uveitisandmultiplesclerosispotentialcommoncausalmutations |