{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T19:22:00Z","timestamp":1789932120624,"version":"4.0.1"},"reference-count":15,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2016,4,16]]},"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec>\n                  <jats:title>The objective of this paper is to<\/jats:title>\n                  <jats:p>describe the phenotype compound heterozygote for mutations in <jats:italic>CECR1<\/jats:italic> in two children. We describe the clinical and immunological phenotype, including the assessment of ADA2 activity, cytokine expression, interferon-stimulated and neutrophil-stimulated gene signatures, and the results of CECR1 sequencing. The first patient presented with intermittent fever, cutaneous vasculitis, myalgia and muscle inflammation on MRI leading to a provisional diagnosis of periarteritis nodosa. Subsequently, two cerebral lacunar lesions were identified following a brain stroke. Clinical features improved on anti-tumour necrosis factor therapy. The first patient's sister demonstrated early-onset, long-lasting anaemia with mild biological inflammation; at the ages of 3 and 5\u2005years, she had presented 2 acute, transient neurological events with lacunar lesions on MRI. CECR1 sequencing identified both sisters to be compound heterozygous for a p.Tyr453Cys mutation and a previously undescribed deletion of exon 7. ADA2 activity was reduced by 50%. Neutrophil-stimulated genes were not overexpressed, but interferon-stimulated genes were. The expression of a panel of other cytokine transcripts was not significantly altered. In conclusion, searching for <jats:italic>CECR1<\/jats:italic> mutation or assessing ADA2 activity should be considered in patients with an atypical presentation of inflammatory disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2015-000236","type":"journal-article","created":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T23:20:18Z","timestamp":1463527218000},"page":"e000236","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":50,"title":["ADA2 deficiency: case report of a new phenotype and novel mutation in two sisters"],"prefix":"10.1136","volume":"2","author":[{"given":"F","family":"Uettwiller","sequence":"first","affiliation":[{"name":"Pediatric Immunology-Hematology and Rheumatology Unit, Institut Imagine, H\u00f4pital Necker-Enfants Malades, Assistance Publique H\u00f4pitaux de Paris, Paris, France"},{"name":"Transversal Unit of Allergology and Rheumatology, CHRU Tours, Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Sarrabay","sequence":"additional","affiliation":[{"name":"Laboratory of Rare and Autoinflammatory Genetic Diseases, CHRU, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M P","family":"Rodero","sequence":"additional","affiliation":[{"name":"INSERM UMR 1163, Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine, H\u00f4pital Necker, Paris Descartes\u2013Sorbonne Paris Cit\u00e9 University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G I","family":"Rice","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Institute of Human Development Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Lagrue","sequence":"additional","affiliation":[{"name":"Inserm U930, CNRS 2448, Tours, France"},{"name":"Service Neurop\u00e9diatrie et Handicaps, CHRU de Tours, Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Marot","sequence":"additional","affiliation":[{"name":"Pediatric Emergency Unit, CHRU Tours, Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Deiva","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, National Referral Center for Neuro-Inflammatory Diseases in Children, H\u00f4pitaux Universitaires Paris Sud, Assistance Publique-H\u00f4pitaux de Paris and UMR 1184, Center for Immunology of viral infections and autoimmune diseases, University Paris Sud, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Touitou","sequence":"additional","affiliation":[{"name":"Laboratory of Rare and Autoinflammatory Genetic Diseases, CHRU, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y J","family":"Crow","sequence":"additional","affiliation":[{"name":"INSERM UMR 1163, Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine, H\u00f4pital Necker, Paris Descartes\u2013Sorbonne Paris Cit\u00e9 University, Paris, France"},{"name":"Manchester Centre for Genomic Medicine, Institute of Human Development Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Quartier","sequence":"additional","affiliation":[{"name":"Pediatric Immunology-Hematology and Rheumatology Unit, Institut Imagine, H\u00f4pital Necker-Enfants Malades, Assistance Publique H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2016,5,17]]},"reference":[{"key":"2025090312250241000_2.1.e000236.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1307361"},{"key":"2025090312250241000_2.1.e000236.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1307362"},{"key":"2025090312250241000_2.1.e000236.3","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20050683"},{"key":"2025090312250241000_2.1.e000236.4","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1016\/j.clinbiochem.2008.10.019","article-title":"Adenosine deaminase in patients with primary immunodeficiency syndromes: the analysis of serum ADA1 and ADA2 activities","volume":"42","author":"Poursharifi","year":"2009","journal-title":"Clin 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correlations","volume":"74","author":"Batu","year":"2015","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"2025090312250241000_2.1.e000236.11","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1136\/annrheumdis-2015-eular.2880","article-title":"Prevalence of CECR1 mutations in pediatric patients with polyarteritis nodosa, livedo reticularis and\/or stroke","volume":"74","author":"Caorsi","year":"2015","journal-title":"Ann Rheum Dis"},{"key":"2025090312250241000_2.1.e000236.12","first-page":"487","article-title":"Enzymes (isoenzyme system) as homeostatic mechanisms the isoenzyme (ADA2) of adenosine deaminase of human monocytes-macrophages as a regulator of the 2\u2032deoxyadenosine","volume":"46","author":"Gakis","year":"1998","journal-title":"Biochem Mol Biol Int"},{"key":"2025090312250241000_2.1.e000236.13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1405506"},{"key":"2025090312250241000_2.1.e000236.14","first-page":"480","article-title":"Mutant ADA2 in 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