Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease.
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and neuronal dysfunction. Although the majority of patients do not present familial aggregation, Mendelian forms have been described. We performed whole-exome sequencing analysis in 132 pati...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Recursos: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/17874 |
| Acesso em linha: | http://hdl.handle.net/20.500.12105/17874 |
| Access Level: | acceso abierto |
| Palavra-chave: | Adult Codon, Nonsense Demyelinating Diseases Exome Female Genetic Predisposition to Disease Humans Inflammation Male Middle Aged Multiple Sclerosis Myelin Sheath Nerve Degeneration Neurons Pedigree Transcriptome Exome Sequencing Young Adult |
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ES_bbbc71e9b8fe0d3d3d592f4da4e568e3 |
|---|---|
| oai_identifier_str |
oai:repisalud.isciii.es:20.500.12105/17874 |
| network_acronym_str |
ES |
| network_name_str |
España |
| spelling |
Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease. Vilariño-Güell, Carles Zimprich, Alexander Martinelli-Boneschi, Filippo Herculano, Bruno Wang, Zhe Matesanz, Fuencisla Urcelay, Elena Vandenbroeck, Koen Leyva, Laura Gris, Denis Massaad, Charbel Quandt, Jacqueline A Traboulsee, Anthony L Encarnacion, Mary Bernales, Cecily Q Follett, Jordan Yee, Irene M Criscuoli, Maria G Deutschländer, Angela Reinthaler, Eva M Zrzavy, Tobias Mascia, Elisabetta Zauli, Andrea Esposito, Federica Alcina, Antonio Izquierdo, Guillermo Espino-Paisán, Laura Mena, Jorge Antigüedad, Alfredo Urbaneja-Romero, Patricia Ortega-Pinazo, Jesús Song, Weihong Sadovnick, A Dessa Adult Codon, Nonsense Demyelinating Diseases Exome Female Genetic Predisposition to Disease Humans Inflammation Male Middle Aged Multiple Sclerosis Myelin Sheath Nerve Degeneration Neurons Pedigree Transcriptome Exome Sequencing Young Adult Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and neuronal dysfunction. Although the majority of patients do not present familial aggregation, Mendelian forms have been described. We performed whole-exome sequencing analysis in 132 patients from 34 multi-incident families, which nominated likely pathogenic variants for MS in 12 genes of the innate immune system that regulate the transcription and activation of inflammatory mediators. Rare missense or nonsense variants were identified in genes of the fibrinolysis and complement pathways (PLAU, MASP1, C2), inflammasome assembly (NLRP12), Wnt signaling (UBR2, CTNNA3, NFATC2, RNF213), nuclear receptor complexes (NCOA3), and cation channels and exchangers (KCNG4, SLC24A6, SLC8B1). These genes suggest a disruption of interconnected immunological and pro-inflammatory pathways as the initial event in the pathophysiology of familial MS, and provide the molecular and biological rationale for the chronic inflammation, demyelination and neurodegeneration observed in MS patients. http://hdl.handle.net/20.500.12105/17874 |
| title |
Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease. |
| spellingShingle |
Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease. Vilariño-Güell, Carles Adult Codon, Nonsense Demyelinating Diseases Exome Female Genetic Predisposition to Disease Humans Inflammation Male Middle Aged Multiple Sclerosis Myelin Sheath Nerve Degeneration Neurons Pedigree Transcriptome Exome Sequencing Young Adult |
| title_short |
Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease. |
| title_full |
Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease. |
| title_fullStr |
Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease. |
| title_full_unstemmed |
Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease. |
| title_sort |
Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease. |
| author |
Vilariño-Güell, Carles |
| author_facet |
Vilariño-Güell, Carles Zimprich, Alexander Martinelli-Boneschi, Filippo Herculano, Bruno Wang, Zhe Matesanz, Fuencisla Urcelay, Elena Vandenbroeck, Koen Leyva, Laura Gris, Denis Massaad, Charbel Quandt, Jacqueline A Traboulsee, Anthony L Encarnacion, Mary Bernales, Cecily Q Follett, Jordan Yee, Irene M Criscuoli, Maria G Deutschländer, Angela Reinthaler, Eva M Zrzavy, Tobias Mascia, Elisabetta Zauli, Andrea Esposito, Federica Alcina, Antonio Izquierdo, Guillermo Espino-Paisán, Laura Mena, Jorge Antigüedad, Alfredo Urbaneja-Romero, Patricia Ortega-Pinazo, Jesús Song, Weihong Sadovnick, A Dessa |
| author_role |
author |
| author2 |
Zimprich, Alexander Martinelli-Boneschi, Filippo Herculano, Bruno Wang, Zhe Matesanz, Fuencisla Urcelay, Elena Vandenbroeck, Koen Leyva, Laura Gris, Denis Massaad, Charbel Quandt, Jacqueline A Traboulsee, Anthony L Encarnacion, Mary Bernales, Cecily Q Follett, Jordan Yee, Irene M Criscuoli, Maria G Deutschländer, Angela Reinthaler, Eva M Zrzavy, Tobias Mascia, Elisabetta Zauli, Andrea Esposito, Federica Alcina, Antonio Izquierdo, Guillermo Espino-Paisán, Laura Mena, Jorge Antigüedad, Alfredo Urbaneja-Romero, Patricia Ortega-Pinazo, Jesús Song, Weihong Sadovnick, A Dessa |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| topic |
Adult Codon, Nonsense Demyelinating Diseases Exome Female Genetic Predisposition to Disease Humans Inflammation Male Middle Aged Multiple Sclerosis Myelin Sheath Nerve Degeneration Neurons Pedigree Transcriptome Exome Sequencing Young Adult |
| topic_facet |
Adult Codon, Nonsense Demyelinating Diseases Exome Female Genetic Predisposition to Disease Humans Inflammation Male Middle Aged Multiple Sclerosis Myelin Sheath Nerve Degeneration Neurons Pedigree Transcriptome Exome Sequencing Young Adult |
| description |
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and neuronal dysfunction. Although the majority of patients do not present familial aggregation, Mendelian forms have been described. We performed whole-exome sequencing analysis in 132 patients from 34 multi-incident families, which nominated likely pathogenic variants for MS in 12 genes of the innate immune system that regulate the transcription and activation of inflammatory mediators. Rare missense or nonsense variants were identified in genes of the fibrinolysis and complement pathways (PLAU, MASP1, C2), inflammasome assembly (NLRP12), Wnt signaling (UBR2, CTNNA3, NFATC2, RNF213), nuclear receptor complexes (NCOA3), and cation channels and exchangers (KCNG4, SLC24A6, SLC8B1). These genes suggest a disruption of interconnected immunological and pro-inflammatory pathways as the initial event in the pathophysiology of familial MS, and provide the molecular and biological rationale for the chronic inflammation, demyelination and neurodegeneration observed in MS patients. |
| publishDate |
2019 |
| format |
article |
| url |
http://hdl.handle.net/20.500.12105/17874 |
| language |
eng |
| eu_rights_str_mv |
openAccess |
| institution |
Instituto de Salud Carlos III (ISCIII) |
| collection |
Repisalud |
| reponame_str |
Repisalud |
| instname_str |
Instituto de Salud Carlos III (ISCIII) |
| _version_ |
1878440003985473536 |
| publishDateSort |
2019 |
| author_browse |
Alcina, Antonio Antigüedad, Alfredo Bernales, Cecily Q Criscuoli, Maria G Deutschländer, Angela Encarnacion, Mary Espino-Paisán, Laura Esposito, Federica Follett, Jordan Gris, Denis Herculano, Bruno Izquierdo, Guillermo Leyva, Laura Martinelli-Boneschi, Filippo Mascia, Elisabetta Massaad, Charbel Matesanz, Fuencisla Mena, Jorge Ortega-Pinazo, Jesús Quandt, Jacqueline A Reinthaler, Eva M Sadovnick, A Dessa Song, Weihong Traboulsee, Anthony L Urbaneja-Romero, Patricia Urcelay, Elena Vandenbroeck, Koen Vilariño-Güell, Carles Wang, Zhe Yee, Irene M Zauli, Andrea Zimprich, Alexander Zrzavy, Tobias |
| score |
6.924472 |