{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:28:10Z","timestamp":1790173690276,"version":"4.1.0"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2015,8,12]],"date-time":"2015-08-12T00:00:00Z","timestamp":1439337600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,8,12]],"date-time":"2015-08-12T00:00:00Z","timestamp":1439337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Hum Genet"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Neonatal diabetes is a highly genetically heterogeneous disorder. There are over 20 distinct syndromic and non-syndromic forms, including dominant, recessive and X-linked subtypes. Biallelic truncating or mis-sense mutations in the DNA-binding domain of the RFX6 transcription factor cause an autosomal recessive, syndromic form of neonatal diabetes previously described as Mitchell\u2013Riley syndrome. In all, eight cases have been reported, with the age at onset of diabetes in the first 2 weeks of life. Here we report two individuals born to double first cousins in whom intestinal atresias consistent with a diagnosis of Mitchell\u2013Riley syndrome were diagnosed at birth, but in whom diabetes did not present until the ages of 3 and 6 years. Novel compound heterozygous <jats:italic>RFX6<\/jats:italic> nonsense mutations (p.Arg726X\/p.Arg866X) were identified at the 3\u2032 end of the gene. The later onset of diabetes in these patients may be due to incomplete inactivation of RFX6. Genetic testing for <jats:italic>RFX6<\/jats:italic> mutations should be considered in patients presenting with intestinal atresias in the absence of neonatal diabetes.<\/jats:p>","DOI":"10.1038\/ejhg.2015.161","type":"journal-article","created":{"date-parts":[[2015,8,12]],"date-time":"2015-08-12T10:22:05Z","timestamp":1439374925000},"page":"1744-1748","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Biallelic RFX6 mutations can cause childhood as well as neonatal onset diabetes mellitus"],"prefix":"10.1038","volume":"23","author":[{"given":"Francis H","family":"Sansbury","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birg\u00fcl","family":"Kirel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Caswell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Lango Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Flanagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T","family":"Hattersley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian","family":"Ellard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J","family":"Shaw-Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,8,12]]},"reference":[{"key":"BFejhg2015161_CR1","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1007\/s00592-011-0331-8","volume":"49","author":"D Iafusco","year":"2012","unstructured":"Iafusco D, Massa O, Pasquino B et al: Minimal incidence of neonatal\/infancy onset diabetes in Italy is 1:90,000 live births. Acta Diabetol 2012; 49: 405\u2013408.","journal-title":"Acta Diabetol"},{"key":"BFejhg2015161_CR2","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1136\/jmg.34.10.838","volume":"34","author":"TG Barrett","year":"1997","unstructured":"Barrett TG, Bundey SE : Wolfram (DIDMOAD) syndrome. J Med Genet 1997; 34: 838\u2013841.","journal-title":"J Med Genet"},{"key":"BFejhg2015161_CR3","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1111\/j.1399-5448.2012.00855.x","volume":"13","author":"C Shaw-Smith","year":"2012","unstructured":"Shaw-Smith C, Flanagan SE, Patch AM et al: Recessive SLC19A2 mutations are a cause of neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia. Pediatr Diabetes 2012; 13: 314\u2013321.","journal-title":"Pediatr Diabetes"},{"key":"BFejhg2015161_CR4","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/ng.1035","volume":"44","author":"H Lango Allen","year":"2011","unstructured":"Lango Allen H, Flanagan SE, Shaw-Smith C et al: GATA6 haploinsufficiency causes pancreatic agenesis in humans. Nat Genet 2011; 44: 20\u201322.","journal-title":"Nat Genet"},{"key":"BFejhg2015161_CR5","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1038\/nature08748","volume":"463","author":"SB Smith","year":"2010","unstructured":"Smith SB, Qu HQ, Taleb N et al: Rfx6 directs islet formation and insulin production in mice and humans. Nature 2010; 463: 776.","journal-title":"Nature"},{"key":"BFejhg2015161_CR6","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1007\/s00125-004-1576-3","volume":"47","author":"J Mitchell","year":"2004","unstructured":"Mitchell J, Punthakee Z, Lo B et al: Neonatal diabetes, with hypoplastic pancreas, intestinal atresia and gall bladder hypoplasia: search for the aetiology of a new autosomal recessive syndrome. Diabetologia 2004; 47: 2160.","journal-title":"Diabetologia"},{"key":"BFejhg2015161_CR7","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1002\/ajmg.a.32304","volume":"146A","author":"L Chappell","year":"2008","unstructured":"Chappell L, Gorman S, Campbell C et al: A Further Example of a Distinctive Autosomal Recessive Syndrome Comprising Neonatal Diabetes Mellitus, Intestinal Atresias and Gall Bladder Agenesis. Am J Med Genet 2008; 146A: 1713.","journal-title":"Am J Med Genet"},{"key":"BFejhg2015161_CR8","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ejmg.2009.10.004","volume":"53","author":"D Martinovici","year":"2010","unstructured":"Martinovici D, Ransy V, Vanden et al: Neonatal hemochromatosis and Martinez-Frias syndrome of intestinal atresia and diabetes mellitus in a consanguineous newborn. Eur J Med Genet 2010; 53: 25.","journal-title":"Eur J Med Genet"},{"key":"BFejhg2015161_CR9","doi-asserted-by":"publisher","first-page":"2821","DOI":"10.1002\/ajmg.a.34251","volume":"155A","author":"R Spiegel","year":"2011","unstructured":"Spiegel R, Dobbie A, Hartman C et al: Clinical characterization of a newly described neonatal diabetes syndrome caused by RFX6 mutations. Am J Med Genet 2011; 155A: 2821.","journal-title":"Am J Med Genet"},{"key":"BFejhg2015161_CR10","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1111\/pedi.12063","volume":"15","author":"RehCS Concepcion JP","year":"2014","unstructured":"Concepcion JP Reh CS, Daniels M et al: Neonatal diabetes, gallbladder agenesis, duodenal atresia, and intestinal malrotation caused by a novel homozygous mutation in RFX6. Pediatr Diabetes. 2014; 15: 67\u201372.","journal-title":"Pediatr Diabetes."},{"key":"BFejhg2015161_CR11","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1007\/s00125-013-2962-5","volume":"56","author":"S Ellard","year":"2013","unstructured":"Ellard S, Lango Allen H, De Franco E et al: Improved genetic testing for monogenic diabetes using targeted next-generation sequencing. 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