Permanent Neonatal Diabetes and Enteric Anendocrinosis Associated With Biallelic Mutations in NEUROG3

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dc.contributor.authorRubio Cabezas, Oscar
dc.contributor.authorJensen, Jan N.
dc.contributor.authorHodgson, Maria I.
dc.contributor.authorCodner, Ethel
dc.contributor.authorEllard, Sian
dc.contributor.authorSerup, Palle
dc.contributor.authorHattersley, Andrew T.
dc.date.accessioned2024-01-10T13:52:00Z
dc.date.available2024-01-10T13:52:00Z
dc.date.issued2011
dc.description.abstractOBJECTIVE-NEUROG3 plays a central role in the development of both pancreatic islets and enteroendocrine cells. Homozygous hypomorphic missense mutations in NEUROG3 have been recently associated with a rare form of congenital malabsolptive diarrhea secondary to enteroendocrine cell dysgenesis. Interestingly, the patients did not develop neonatal diabetes but childhood-onset diabetes. We hypothesized that null mutations in NEUROG3 might be responsible for the disease in a patient with permanent neonatal diabetes and severe congenital malabsorptive diarrhea.
dc.description.abstractRESEARCH DESIGN AND METHODS The single coding exon of NEUROG3 was amplified and sequenced from genomic DNA. The mutant protein isoforms were functionally characterized by measuring their ability to bind to an E-box element in the NEUROD1 promoter in vitro and to induce ectopic endocrine cell formation and cell delamination after in ovo chicken endoderm electroporation.
dc.description.abstractRESULTS Two different heterozygous point mutations in NEUROG3 were identified in the proband [c.82G > T (p.E28X) and c.404T > C (p.L135P)], each being inherited from an unaffected parent. Both in vitro and in vivo functional studies indicated that the mutant isoforms are biologically inactive. In keeping with this, no enteroendocrine cells were detected in intestinal biopsy samples from the patient.
dc.description.abstractCONCLUSIONS Severe deficiency of neurogenin 3 causes a rare novel subtype of permanent neonatal diabetes. This finding confirms the essential role of NEUROG3 in islet development and function in humans. Diabetes 60:1349-1353, 2011
dc.description.funderEuropean Union
dc.description.funderWellcome Trust
dc.description.funderInstituto de Salud Carlos III
dc.description.funderJuvenile Diabetes Research Foundation
dc.description.funderNational Institute for Health Research funded Peninsula Clinical Research Facility
dc.fechaingreso.objetodigital2024-05-22
dc.format.extent5 páginas
dc.fuente.origenWOS
dc.identifier.doi10.2337/db10-1008
dc.identifier.eissn1939-327X
dc.identifier.issn0012-1797
dc.identifier.pubmedidMEDLINE:21378176
dc.identifier.urihttps://doi.org/10.2337/db10-1008
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79638
dc.identifier.wosidWOS:000289496100031
dc.information.autorucMedicina;Hodgson M;S/I;99461
dc.issue.numero4
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final1353
dc.pagina.inicio1349
dc.publisherAMER DIABETES ASSOC
dc.revistaDIABETES
dc.rightsacceso abierto
dc.subjectCOMMON-CAUSE
dc.subjectMUTANT NEUROGENIN-3
dc.subjectGENE
dc.subjectMELLITUS
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePermanent Neonatal Diabetes and Enteric Anendocrinosis Associated With Biallelic Mutations in NEUROG3
dc.typeartículo
dc.volumen60
sipa.codpersvinculados99461
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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