{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:05:52Z","timestamp":1792047952760,"version":"4.4.0"},"reference-count":39,"publisher":"American Academy of Pediatrics (AAP)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,4,1]]},"abstract":"<jats:p>Germline mutations in the SLC29A3 gene result in a range of recessive, clinically related syndromes: H syndrome, pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome, Faisalabad histiocytosis, and sinus histiocytosis with massive lymphadenopathy. The main symptoms of these diseases are hyperpigmentation with hypertrichosis, sensorineural deafness, diabetes, short stature, uveitis, and Rosai-Dorfman like histiocytosis. Here, we report the case of an 11-month-old boy with early-onset, recurrent episodes of unprovoked fever lasting 7 to 10 days and associated with pericardial effusion, abdominal pain, diarrhea, and inflammation. Physical examination revealed hyperpigmentation with hypertrichosis, dysmorphic features, and spleen and liver enlargement. Failure to thrive, sensorineural deafness, retarded psychomotor development, and a Rosai-Dorfman like cheek lesion developed subsequently. The febrile episodes did not respond to tumor necrosis factor \u03b1 antagonists and interleukin-1. Sequencing of the SLC29A3 gene revealed a homozygous missense mutation c.1088G&amp;gt;A (p.Arg363Gln). These observations suggest that a newly identified mutation in the SLC29A3 gene may be associated with an autoinflammatory disorder. Genetic defects in SLC29A3 should be considered in patients with autoinflammatory manifestations, recurrent febrile attacks, and 1 or more of the symptoms found in the broad spectrum of SLC29A3-related disorders (especially hyperpigmentation with hypertrichosis).<\/jats:p>","DOI":"10.1542\/peds.2012-2255","type":"journal-article","created":{"date-parts":[[2013,3,25]],"date-time":"2013-03-25T22:07:46Z","timestamp":1364249266000},"page":"e1308-e1313","source":"Crossref","is-referenced-by-count":71,"title":["Mutation in the\n                    <i>SLC29A3<\/i>\n                    Gene: A New Cause of a Monogenic, Autoinflammatory Condition"],"prefix":"10.1542","volume":"131","author":[{"given":"Isabelle","family":"Melki","sequence":"first","affiliation":[{"name":"Departments of Pediatric Immunology, Hematology, and Rheumatology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Lambot","sequence":"additional","affiliation":[{"name":"Pediatric Radiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Jonard","sequence":"additional","affiliation":[{"name":"Department of Genetics, APHP, Trousseau Hospital, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Couloigner","sequence":"additional","affiliation":[{"name":"Microbiology, APHP, Necker Hospital, Paris, France;"},{"name":"Paris Descartes University, Sorbonne Paris Cit\u00e9, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Quartier","sequence":"additional","affiliation":[{"name":"Departments of Pediatric Immunology, Hematology, and Rheumatology,"},{"name":"Paris Descartes University, Sorbonne Paris Cit\u00e9, Paris, France;"},{"name":"Institut IMAGINE, Paris, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Neven","sequence":"additional","affiliation":[{"name":"Departments of Pediatric Immunology, Hematology, and Rheumatology,"},{"name":"Paris Descartes University, Sorbonne Paris Cit\u00e9, Paris, France;"},{"name":"Institut IMAGINE, Paris, France; and"},{"name":"INSERM U768, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Bader-Meunier","sequence":"additional","affiliation":[{"name":"Departments of Pediatric Immunology, Hematology, and Rheumatology,"},{"name":"Institut IMAGINE, Paris, France; and"},{"name":"INSERM U768, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2013,4,1]]},"reference":[{"key":"2021120903065018400_B1","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev.immunol.25.022106.141627","article-title":"Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*).","volume":"27","author":"Masters","year":"2009","journal-title":"Annu Rev Immunol"},{"issue":"3","key":"2021120903065018400_B2","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/j.1365-2249.2011.04533.x","article-title":"Immunology in clinic review series; focus on autoinflammatory diseases: update on monogenic autoinflammatory diseases: the role of interleukin (IL)-1 and an emerging role for cytokines beyond IL-1.","volume":"167","author":"Goldbach-Mansky","year":"2012","journal-title":"Clin Exp Immunol"},{"issue":"7","key":"2021120903065018400_B3","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1182\/blood-2003-07-2531","article-title":"Molecular basis of the spectral expression of CIAS1 mutations associated with phagocytic cell-mediated autoinflammatory disorders CINCA\/NOMID, MWS, and FCU.","volume":"103","author":"Neven","year":"2004","journal-title":"Blood"},{"issue":"2","key":"2021120903065018400_B4","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s00247-006-0358-0","article-title":"Arthropathy of neonatal onset multisystem inflammatory disease (NOMID\/CINCA).","volume":"37","author":"Hill","year":"2007","journal-title":"Pediatr Radiol"},{"issue":"23","key":"2021120903065018400_B5","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1056\/NEJMoa0810787","article-title":"Use of canakinumab in the cryopyrin-associated periodic syndrome.","volume":"360","author":"Lachmann","year":"2009","journal-title":"N Engl J Med"},{"issue":"1","key":"2021120903065018400_B6","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/art.25057","article-title":"Long-term efficacy of the interleukin-1 receptor antagonist anakinra in ten patients with neonatal-onset multisystem inflammatory disease\/chronic infantile neurologic, cutaneous, articular syndrome.","volume":"62","author":"Neven","year":"2010","journal-title":"Arthritis Rheum"},{"issue":"23","key":"2021120903065018400_B7","doi-asserted-by":"crossref","first-page":"2426","DOI":"10.1056\/NEJMoa0807865","article-title":"An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist.","volume":"360","author":"Aksentijevich","year":"2009","journal-title":"N Engl J Med"},{"issue":"5","key":"2021120903065018400_B8","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1073\/pnas.0708616105","article-title":"Mutations in NALP12 cause hereditary periodic fever syndromes.","volume":"105","author":"J\u00e9ru","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"issue":"5","key":"2021120903065018400_B9","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1093\/ndt\/gfr528","article-title":"Dramatic beneficial effect of interleukin-1 inhibitor treatment in patients with familial Mediterranean fever complicated with amyloidosis and renal failure.","volume":"27","author":"Stankovic Stojanovic","year":"2012","journal-title":"Nephrol Dial Transplant"},{"issue":"1","key":"2021120903065018400_B10","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2010-3639","article-title":"Mevalonate kinase deficiency: a survey of 50 patients.","volume":"128","author":"Bader-Meunier","year":"2011","journal-title":"Pediatrics"},{"issue":"3","key":"2021120903065018400_B11","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1002\/art.33368","article-title":"Mutations in proteasome subunit \u03b2 type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity.","volume":"64","author":"Liu","year":"2012","journal-title":"Arthritis Rheum"},{"issue":"8","key":"2021120903065018400_B12","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1038\/ng1842","article-title":"Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Gouti\u00e8res syndrome and mimic congenital viral brain infection.","volume":"38","author":"Crow","year":"2006","journal-title":"Nat Genet"},{"issue":"8","key":"2021120903065018400_B13","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/ng1845","article-title":"Mutations in the gene encoding the 3\u2032-5\u2032 DNA exonuclease TREX1 cause Aicardi-Gouti\u00e8res syndrome at the AGS1 locus.","volume":"38","author":"Crow","year":"2006","journal-title":"Nat Genet"},{"issue":"7","key":"2021120903065018400_B14","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/ng.373","article-title":"Mutations involved in Aicardi-Gouti\u00e8res syndrome implicate SAMHD1 as regulator of the innate immune response.","volume":"41","author":"Rice","year":"2009","journal-title":"Nat Genet"},{"issue":"5","key":"2021120903065018400_B15","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1111\/j.1525-1470.2010.01163.x","article-title":"Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome: a case report.","volume":"28","author":"Ramot","year":"2011","journal-title":"Pediatr Dermatol"},{"issue":"6","key":"2021120903065018400_B16","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.ajhg.2010.10.031","article-title":"PSMB8 encoding the \u03b25i proteasome subunit is mutated in joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndrome.","volume":"87","author":"Agarwal","year":"2010","journal-title":"Am J Hum Genet"},{"issue":"36","key":"2021120903065018400_B17","doi-asserted-by":"crossref","first-page":"14914","DOI":"10.1073\/pnas.1106015108","article-title":"Proteasome assembly defect due to a proteasome subunit beta type 8 (PSMB8) mutation causes the autoinflammatory disorder, Nakajo-Nishimura syndrome.","volume":"108","author":"Arima","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"2021120903065018400_B18","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jaad.2008.03.021","article-title":"The H syndrome: a genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations.","volume":"59","author":"Molho-Pessach","year":"2008","journal-title":"J Am Acad Dermatol"},{"issue":"4","key":"2021120903065018400_B19","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.ajhg.2008.09.013","article-title":"The H syndrome is caused by mutations in the nucleoside transporter hENT3.","volume":"83","author":"Molho-Pessach","year":"2008","journal-title":"Am J Hum Genet"},{"issue":"2","key":"2021120903065018400_B20","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/j.1525-1470.2007.00352.x","article-title":"Pigmented hypertrichotic dermatosis and insulin dependent diabetes: manifestations of a unique genetic disorder?","volume":"24","author":"Prendiville","year":"2007","journal-title":"Pediatr Dermatol"},{"issue":"12","key":"2021120903065018400_B21","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1093\/hmg\/ddp161","article-title":"SLC29A3 gene is mutated in pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome and interacts with the insulin signaling pathway.","volume":"18","author":"Cliffe","year":"2009","journal-title":"Hum Mol Genet"},{"issue":"5","key":"2021120903065018400_B22","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1086\/301824","article-title":"Autozygosity mapping, to chromosome 11q25, of a rare autosomal recessive syndrome causing histiocytosis, joint contractures, and sensorineural deafness.","volume":"62","author":"Moynihan","year":"1998","journal-title":"Am J Hum Genet"},{"issue":"2","key":"2021120903065018400_B23","doi-asserted-by":"crossref","first-page":"e1000833","DOI":"10.1371\/journal.pgen.1000833","article-title":"Mutations in SLC29A3, encoding an equilibrative nucleoside transporter ENT3, cause a familial histiocytosis syndrome (Faisalabad histiocytosis) and familial Rosai-Dorfman disease.","volume":"6","author":"Morgan","year":"2010","journal-title":"PLoS Genet"},{"issue":"5","key":"2021120903065018400_B24","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ejmg.2010.06.012","article-title":"Expanding the clinical spectrum of SLC29A3 gene defects.","volume":"53","author":"Spiegel","year":"2010","journal-title":"Eur J Med Genet"},{"issue":"1","key":"2021120903065018400_B25","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/DAD.0b013e3181ee547c","article-title":"A case of H syndrome showing immunophenotye similarities to Rosai-Dorfman disease.","volume":"33","author":"Avitan-Hersh","year":"2011","journal-title":"Am J Dermatopathol"},{"issue":"1","key":"2021120903065018400_B26","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ejmg.2011.06.009","article-title":"Progressive hearing loss associated with a unique cervical node due to a homozygous SLC29A3 mutation: a very mild phenotype.","volume":"55","author":"Jonard","year":"2012","journal-title":"Eur J Med Genet"},{"issue":"1","key":"2021120903065018400_B27","doi-asserted-by":"crossref","first-page":"e29708","DOI":"10.1371\/journal.pone.0029708","article-title":"A mild form of SLC29A3 disorder: a frameshift deletion leads to the paradoxical translation of an otherwise noncoding mRNA splice variant.","volume":"7","author":"Bolze","year":"2012","journal-title":"PLoS ONE"},{"issue":"1","key":"2021120903065018400_B28","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jdermsci.2009.09.011","article-title":"The H syndrome: two novel mutations affecting the same amino acid residue of hENT3.","volume":"57","author":"Molho-Pessach","year":"2010","journal-title":"J Dermatol Sci"},{"issue":"7","key":"2021120903065018400_B29","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.ijporl.2010.03.053","article-title":"Early-onset sensorineural hearing loss is a prominent feature of H syndrome.","volume":"74","author":"Ramot","year":"2010","journal-title":"Int J Pediatr Otorhinolaryngol"},{"issue":"1","key":"2021120903065018400_B30","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1525-1470.2009.01076.x","article-title":"The H syndrome.","volume":"27","author":"El-Khateeb","year":"2010","journal-title":"Pediatr Dermatol"},{"issue":"5","key":"2021120903065018400_B31","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1111\/j.1365-2133.2010.09653.x","article-title":"H syndrome: novel and recurrent mutations in SLC29A3.","volume":"162","author":"Priya","year":"2010","journal-title":"Br J Dermatol"},{"issue":"3","key":"2021120903065018400_B32","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1399-5448.2008.00470.x","article-title":"Diabetes mellitus, exocrine pancreatic deficiency, hypertrichosis, hyperpigmentation, and chronic inflammation: confirmation of a syndrome.","volume":"10","author":"Hussain","year":"2009","journal-title":"Pediatr Diabetes"},{"issue":"4","key":"2021120903065018400_B33","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/j.1442-200x.2005.02096.x","article-title":"Sinus histiocytosis with massive lymphadenopathy in three brothers.","volume":"47","author":"Kismet","year":"2005","journal-title":"Pediatr Int"},{"issue":"5","key":"2021120903065018400_B34","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1002\/pbc.20605","article-title":"Faisalabad histiocytosis mimics Rosai-Dorfman disease: brothers with lymphadenopathy, intrauterine fractures, short stature, and sensorineural deafness.","volume":"47","author":"Rossbach","year":"2006","journal-title":"Pediatr Blood Cancer"},{"issue":"16","key":"2021120903065018400_B35","doi-asserted-by":"crossref","first-page":"15880","DOI":"10.1074\/jbc.M414337200","article-title":"Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes.","volume":"280","author":"Baldwin","year":"2005","journal-title":"J Biol Chem"},{"issue":"10","key":"2021120903065018400_B36","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1111\/j.1349-7006.2007.00581.x","article-title":"Cellular localization and functional characterization of the equilibrative nucleoside transporters of antitumor nucleosides.","volume":"98","author":"Endo","year":"2007","journal-title":"Cancer Sci"},{"issue":"4","key":"2021120903065018400_B37","doi-asserted-by":"crossref","first-page":"G910","DOI":"10.1152\/ajpgi.90672.2008","article-title":"Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by human equilibrative nucleoside transporter-3.","volume":"296","author":"Govindarajan","year":"2009","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"36","key":"2021120903065018400_B38","doi-asserted-by":"crossref","first-page":"28343","DOI":"10.1074\/jbc.M110.109199","article-title":"Human equilibrative nucleoside transporter-3 (hENT3) spectrum disorder mutations impair nucleoside transport, protein localization, and stability.","volume":"285","author":"Kang","year":"2010","journal-title":"J Biol Chem"},{"issue":"6064","key":"2021120903065018400_B39","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1126\/science.1213682","article-title":"Equilibrative nucleoside transporter 3 deficiency perturbs lysosome function and macrophage homeostasis.","volume":"335","author":"Hsu","year":"2012","journal-title":"Science"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/131\/4\/e1308\/1099198\/peds_2012-2255.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/131\/4\/e1308\/1099198\/peds_2012-2255.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T11:58:09Z","timestamp":1639051089000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/131\/4\/e1308\/31799\/Mutation-in-the-SLC29A3-Gene-A-New-Cause-of-a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,1]]},"references-count":39,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2013,4,1]]},"published-print":{"date-parts":[[2013,4,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2012-2255","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.717996638.793474009","asserted-by":"object"}]},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,1]]}}}