{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:07:22Z","timestamp":1790312842389,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,3,28]],"date-time":"2016-03-28T00:00:00Z","timestamp":1459123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Blau syndrome is characterized by noncaseating granulomatous arthritis, dermatitis, and uveitis, and results from gain\u2010of\u2010function <jats:italic>NOD2<\/jats:italic> mutations. This study was undertaken to identify the genetic cause of the disease in a family with 3 members with Blau syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied a family with 3 affected members across 2 consecutive generations. The children's symptoms started early (at 6 and 7 months of age) and included polyarthritis, dermatitis, uveitis, and fever. In contrast, the father's symptoms started later (at 22 years of age) and included noncaseating granulomatous dermatitis and uveitis. We analyzed the <jats:italic>NOD2<\/jats:italic> gene in all patients by both the Sanger method of DNA sequencing and amplicon\u2010based deep sequencing using an Ion Torrent PGM platform.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sanger chromatograms revealed the heterozygous c.1001G&gt;A transition in both children, which resulted in the p.Arg334Gln mutation that causes Blau syndrome. In contrast, the father's chromatograms revealed a small peak of adenine at the c.1001 position, suggesting the presence of a somatic <jats:italic>NOD2<\/jats:italic> mutation. To evaluate this hypothesis, we performed amplicon\u2010based deep sequencing using DNA from different tissues, which confirmed a variable degree (0.9\u201312.9%) of somatic <jats:italic>NOD2<\/jats:italic> mosaicism. The previous detection of the <jats:italic>NOD2<\/jats:italic> mutation in his daughters strongly suggests the presence of gonosomal (somatic plus gonadal) <jats:italic>NOD2<\/jats:italic> mosaicism in the father. Comparative analyses with Blau syndrome patients carrying the germline p.Arg334Gln <jats:italic>NOD2<\/jats:italic> mutation revealed late onset of the disease, a mild inflammatory phenotype, and an absence of complications in patients with <jats:italic>NOD2<\/jats:italic> mosaicism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first description of gonosomal <jats:italic>NOD2<\/jats:italic> mosaicism as the cause of intrafamilial recurrence of Blau syndrome. Our findings also indicate that Blau syndrome includes more diverse and milder phenotypes than previously described.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39519","type":"journal-article","created":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T11:27:04Z","timestamp":1448450824000},"page":"1039-1044","source":"Crossref","is-referenced-by-count":59,"title":["Brief Report: First Identification of Intrafamilial Recurrence of Blau Syndrome due to Gonosomal <i>NOD2<\/i> Mosaicism"],"prefix":"10.1002","volume":"68","author":[{"given":"Anna","family":"Mensa\u2010Vilaro","sequence":"first","affiliation":[{"name":"Hospital Clinic\u2013Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weng","family":"Tarng Cham","sequence":"additional","affiliation":[{"name":"Selayang Hospital Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swee","family":"Ping Tang","sequence":"additional","affiliation":[{"name":"Selayang Hospital Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sern","family":"Chin Lim","sequence":"additional","affiliation":[{"name":"Selayang Hospital Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Gonz\u00e1lez\u2010Roca","sequence":"additional","affiliation":[{"name":"Hospital Clinic\u2013Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estibaliz","family":"Ruiz\u2010Ortiz","sequence":"additional","affiliation":[{"name":"Hospital Clinic\u2013Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roziana","family":"Ariffin","sequence":"additional","affiliation":[{"name":"Kuala Lumpur Hospital Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Yag\u00fce","sequence":"additional","affiliation":[{"name":"Hospital Clinic\u2013Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan I.","family":"Ar\u00f3stegui","sequence":"additional","affiliation":[{"name":"Hospital Clinic\u2013Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24533"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22966"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng720"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-07-2972"},{"key":"e_1_2_7_6_1","unstructured":"International Society for Systemic AutoInflammatory Fevers. 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