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http://hdl.handle.net/2445/105538
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DC Field | Value | Language |
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dc.contributor.author | Nakagawa, Kenji | - |
dc.contributor.author | Gonzalez Roca, Eva | - |
dc.contributor.author | Souto, Alejandro | - |
dc.contributor.author | Kawai, Toshinao | - |
dc.contributor.author | Umebayashi, Hiroaki | - |
dc.contributor.author | Campistol Plana, Jaume | - |
dc.contributor.author | Cañellas, Jeronima | - |
dc.contributor.author | Takei, Syuji | - |
dc.contributor.author | Kobayashi, Norimoto | - |
dc.contributor.author | Callejas Rubio, José Luis | - |
dc.contributor.author | Ortego Centeno, Norberto | - |
dc.contributor.author | Ruiz Ortiz, Estíbaliz | - |
dc.contributor.author | Rius, Fina | - |
dc.contributor.author | Antón López, Jordi | - |
dc.contributor.author | Iglesias Jiménez, Estíbaliz | - |
dc.contributor.author | Jiménez Treviño, Santiago | - |
dc.contributor.author | Vargas, Carmen | - |
dc.contributor.author | Fernandez Martin, Julian | - |
dc.contributor.author | Calvo, Inmaculada | - |
dc.contributor.author | Hernández Rodríguez, José | - |
dc.contributor.author | Méndez, María | - |
dc.contributor.author | Dordal, María Teresa | - |
dc.contributor.author | Basagaña, Maria | - |
dc.contributor.author | Buján Rivas, Segundo | - |
dc.contributor.author | Yashiro, Masato | - |
dc.contributor.author | Kubota, Tetsuo | - |
dc.contributor.author | Koike, Ryuji | - |
dc.contributor.author | Akuta, Naoko | - |
dc.contributor.author | Shimoyama, Kumiko | - |
dc.contributor.author | Iwata, Naomi | - |
dc.contributor.author | Saito, Megumu K. | - |
dc.contributor.author | Ohara, Osamu | - |
dc.contributor.author | Kambe, Naotomo | - |
dc.contributor.author | Yasumi, Takahiro | - |
dc.contributor.author | Izawa, Kazushi | - |
dc.contributor.author | Kawai, Tomoki | - |
dc.contributor.author | Heike, Toshio | - |
dc.contributor.author | Yagüe, Jordi | - |
dc.contributor.author | Nishikomori, Ryuta | - |
dc.contributor.author | Aróstegui Gorospe, Juan Ignacio | - |
dc.date.accessioned | 2017-01-12T16:02:26Z | - |
dc.date.available | 2017-01-12T16:02:26Z | - |
dc.date.issued | 2015-03 | - |
dc.identifier.issn | 0003-4967 | - |
dc.identifier.uri | http://hdl.handle.net/2445/105538 | - |
dc.description.abstract | Familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome are dominantly inherited autoinflammatory diseases associated to gain-of-function NLRP3 mutations and included in the cryopyrin-associated periodic syndromes (CAPS). A variable degree of somatic NLRP3 mosaicism has been detected in ≈35% of patients with CINCA. However, no data are currently available regarding the relevance of this mechanism in other CAPS phenotypes. OBJECTIVE: To evaluate somatic NLRP3 mosaicism as the disease-causing mechanism in patients with clinical CAPS phenotypes other than CINCA and NLRP3 mutation-negative. METHODS: NLRP3 analyses were performed by Sanger sequencing and by massively parallel sequencing. Apoptosis-associated Speck-like protein containing a CARD (ASC)-dependent nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB) activation and transfection-induced THP-1 cell death assays determined the functional consequences of the detected variants. RESULTS: A variable degree (5.5-34.9%) of somatic NLRP3 mosaicism was detected in 12.5% of enrolled patients, all of them with a MWS phenotype. Six different missense variants, three novel (p.D303A, p.K355T and p.L411F), were identified. Bioinformatics and functional analyses confirmed that they were disease-causing, gain-of-function NLRP3 mutations. All patients treated with anti-interleukin1 drugs showed long-lasting positive responses. CONCLUSIONS: We herein show somatic NLRP3 mosaicism underlying MWS, probably representing a shared genetic mechanism in CAPS not restricted to CINCA syndrome. The data here described allowed definitive diagnoses of these patients, which had serious implications for gaining access to anti-interleukin 1 treatments under legal indication and for genetic counselling. The detection of somatic mosaicism is difficult when using conventional methods. Potential candidates should benefit from the use of modern genetic tools | - |
dc.format.extent | 9 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | BMJ Publishing Group | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1136/annrheumdis-2013-204361 | - |
dc.relation.ispartof | Annals of the Rheumatic Diseases, 2015, vol. 74, num. 3, p. 603-610 | - |
dc.relation.uri | https://doi.org/10.1136/annrheumdis-2013-204361 | - |
dc.rights | (c) BMJ Publishing Group, 2015 | - |
dc.source | Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques) | - |
dc.subject.classification | Genètica molecular | - |
dc.subject.classification | Malalties hereditàries | - |
dc.subject.classification | Genètica mèdica | - |
dc.subject.classification | Inflamació | - |
dc.subject.other | Molecular genetics | - |
dc.subject.other | Genetic diseases | - |
dc.subject.other | Medical genetics | - |
dc.subject.other | Inflammation | - |
dc.title | Somatic NLRP3 mosaicism in Muckle-Wells syndrome. A genetic mechanism shared by different phenotypes of cryopyrin-associated periodic syndromes | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 640866 | - |
dc.date.updated | 2017-01-12T16:02:26Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 24326009 | - |
Appears in Collections: | Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques) |
Files in This Item:
File | Description | Size | Format | |
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640866.pdf | 1.25 MB | Adobe PDF | View/Open |
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