2026-06-14T05:05:21Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/178742024-09-21T20:32:09Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16969
Repisalud author Vilariño-Güell, Carles author Zimprich, Alexander author Martinelli-Boneschi, Filippo author Herculano, Bruno author Wang, Zhe author Matesanz, Fuencisla author Urcelay, Elena author Vandenbroeck, Koen author Leyva, Laura author Gris, Denis author Massaad, Charbel author Quandt, Jacqueline A author Traboulsee, Anthony L author Encarnacion, Mary author Bernales, Cecily Q author Follett, Jordan author Yee, Irene M author Criscuoli, Maria G author Deutschländer, Angela author Reinthaler, Eva M author Zrzavy, Tobias author Mascia, Elisabetta author Zauli, Andrea author Esposito, Federica author Alcina, Antonio author Izquierdo, Guillermo author Espino-Paisán, Laura author Mena, Jorge author Antigüedad, Alfredo author Urbaneja-Romero, Patricia author Ortega-Pinazo, Jesús author Song, Weihong author Sadovnick, A Dessa 2024-02-10T20:01:38Z 2024-02-10T20:01:38Z 2019-06-06 10.1371/journal.pgen.1008180 1553-7404 PLoS genetics http://hdl.handle.net/10668/14080 31170158 http://hdl.handle.net/20.500.12105/17874 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. eng Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease. research article