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dc.contributor.authorDe Franco, E
dc.contributor.authorShaw-Smith, C
dc.contributor.authorFlanagan, SE
dc.contributor.authorShepherd, MH
dc.contributor.authorHattersley, AT
dc.contributor.authorEllard, S
dc.date.accessioned2019-11-08T12:14:29Z
dc.date.issued2012-12-06
dc.description.abstractWe recently reported de novo GATA6 mutations as the most common cause of pancreatic agenesis, accounting for 15 of 27 (56%) patients with insulin-treated neonatal diabetes and exocrine pancreatic insufficiency requiring enzyme replacement therapy. We investigated the role of GATA6 mutations in 171 subjects with neonatal diabetes of unknown genetic etiology from a cohort of 795 patients with neonatal diabetes. Mutations in known genes had been confirmed in 624 patients (including 15 GATA6 mutations). Sequencing of the remaining 171 patients identified nine new case subjects (24 of 795, 3%). Pancreatic agenesis was present in 21 case subjects (six new); two patients had permanent neonatal diabetes with no enzyme supplementation and one had transient neonatal diabetes. Four parents with heterozygous GATA6 mutations were diagnosed with diabetes outside the neonatal period (12-46 years). Subclinical exocrine insufficiency was demonstrated by low fecal elastase in three of four diabetic patients who did not receive enzyme supplementation. One parent with a mosaic mutation was not diabetic but had a heart malformation. Extrapancreatic features were observed in all 24 probands and three parents, with congenital heart defects most frequent (83%). Heterozygous GATA6 mutations cause a wide spectrum of diabetes manifestations, ranging from pancreatic agenesis to adult-onset diabetes with subclinical or no exocrine insufficiency. Copyright © 2013 by the American Diabetes Association.en_GB
dc.description.sponsorshipEuropean Union FP7en_GB
dc.description.sponsorshipWellcome Trusten_GB
dc.identifier.citationVol. 62 (3), pp. 993 - 997en_GB
dc.identifier.doi10.2337/db12-0885
dc.identifier.grantnumberFP7-PEOPLE-ITN-2008en_GB
dc.identifier.grantnumber223211en_GB
dc.identifier.urihttp://hdl.handle.net/10871/39569
dc.language.isoenen_GB
dc.publisherAmerican Diabetes Associationen_GB
dc.rights© 2013 by the American Diabetes Association. Open access. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See https://creativecommons.org/licenses/by-nc-nd/3.0/ for details.en_GB
dc.titleGATA6 mutations cause a broad phenotypic spectrum of diabetes from pancreatic agenesis to adult-onset diabetes without exocrine insufficiencyen_GB
dc.typeArticleen_GB
dc.date.available2019-11-08T12:14:29Z
dc.identifier.issn0012-1797
dc.descriptionThis is the final version. Available on open access from the American Diabetes Association via the DOI in this recorden_GB
dc.identifier.journalDiabetesen_GB
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/en_GB
pubs.euro-pubmed-idMED:23223019
dcterms.dateAccepted2012-09-30
rioxxterms.versionVoRen_GB
rioxxterms.licenseref.startdate2012-12-06
rioxxterms.typeJournal Article/Reviewen_GB
refterms.dateFCD2019-11-08T12:11:41Z
refterms.versionFCDVoR
refterms.dateFOA2019-11-08T12:14:33Z
refterms.panelAen_GB


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© 2013 by the American Diabetes Association. Open access. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See https://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
Except where otherwise noted, this item's licence is described as © 2013 by the American Diabetes Association. Open access. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See https://creativecommons.org/licenses/by-nc-nd/3.0/ for details.