Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia.

2.50
Hdl Handle:
http://hdl.handle.net/11287/615781
Title:
Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia.
Authors:
Colclough, K.; Bellanne-Chantelot, C.; Saint-Martin, C.; Flanagan, Sarah; Ellard, Sian ( 0000-0002-7620-5526 )
Abstract:
Maturity-onset diabetes of the young (MODY) is a monogenic disorder characterized by autosomal dominant inheritance of young-onset (typically <25 years), noninsulin-dependent diabetes due to defective insulin secretion. MODY is both clinically and genetically heterogeneous with mutations in at least 10 genes. Mutations in the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are the most common cause of MODY in most adult populations studied. The number of different pathogenic HNF1A mutations totals 414 in 1,247 families. Mutations in the HNF4A gene encoding hepatocyte nuclear factor-4 alpha are a rarer cause of MODY with 103 different mutations reported in 173 families to date. Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. The HNF4A MODY phenotype has been expanded by the reports of macrosomia in ∼50% of babies, and more rarely, neonatal hyperinsulinemic hypoglycemia. The identification of an HNF1A or HNF4A gene mutation has important implications for clinical management in diabetes and pregnancy, but MODY is significantly underdiagnosed. Current research is focused on identifying biomarkers and developing probability models to identify those patients most likely to have MODY, until next generation sequencing technology enables cost-effective gene analysis for all patients with young onset diabetes.
Citation:
Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia. 2013, 34 (5):669-85 Hum. Mutat.
Publisher:
Wiley
Journal:
Human mutation
Issue Date:
May-2013
URI:
http://hdl.handle.net/11287/615781
DOI:
10.1002/humu.22279
PubMed ID:
23348805
Additional Links:
http://onlinelibrary.wiley.com/doi/10.1002/humu.22279/abstract;jsessionid=A112B5D6E3FDD446FE277BC03AF5E006.f02t01
Note:
RD&E staff can access the full-text of this article via OpenAccess. Click on the ‘Additional Link’ above to access the full-text and log in with NHS OpenAthens if propted.
Type:
Journal Article
Language:
en
ISSN:
1098-1004
Appears in Collections:
pre-2014 RD&E publications; Clinical Genetics (Peninsula Genetics); Honorary contracts publications

Full metadata record

DC FieldValue Language
dc.contributor.authorColclough, K.en
dc.contributor.authorBellanne-Chantelot, C.en
dc.contributor.authorSaint-Martin, C.en
dc.contributor.authorFlanagan, Sarahen
dc.contributor.authorEllard, Sianen
dc.date.accessioned2016-07-08T08:58:29Z-
dc.date.available2016-07-08T08:58:29Z-
dc.date.issued2013-05-
dc.identifier.citationMutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia. 2013, 34 (5):669-85 Hum. Mutat.en
dc.identifier.issn1098-1004-
dc.identifier.pmid23348805-
dc.identifier.doi10.1002/humu.22279-
dc.identifier.urihttp://hdl.handle.net/11287/615781-
dc.description.abstractMaturity-onset diabetes of the young (MODY) is a monogenic disorder characterized by autosomal dominant inheritance of young-onset (typically <25 years), noninsulin-dependent diabetes due to defective insulin secretion. MODY is both clinically and genetically heterogeneous with mutations in at least 10 genes. Mutations in the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are the most common cause of MODY in most adult populations studied. The number of different pathogenic HNF1A mutations totals 414 in 1,247 families. Mutations in the HNF4A gene encoding hepatocyte nuclear factor-4 alpha are a rarer cause of MODY with 103 different mutations reported in 173 families to date. Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. The HNF4A MODY phenotype has been expanded by the reports of macrosomia in ∼50% of babies, and more rarely, neonatal hyperinsulinemic hypoglycemia. The identification of an HNF1A or HNF4A gene mutation has important implications for clinical management in diabetes and pregnancy, but MODY is significantly underdiagnosed. Current research is focused on identifying biomarkers and developing probability models to identify those patients most likely to have MODY, until next generation sequencing technology enables cost-effective gene analysis for all patients with young onset diabetes.en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://onlinelibrary.wiley.com/doi/10.1002/humu.22279/abstract;jsessionid=A112B5D6E3FDD446FE277BC03AF5E006.f02t01en
dc.rightsArchived with thanks to Human mutationen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleMutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia.en
dc.typeJournal Articleen
dc.identifier.journalHuman mutationen
dc.description.noteRD&E staff can access the full-text of this article via OpenAccess. Click on the ‘Additional Link’ above to access the full-text and log in with NHS OpenAthens if propted.en
dc.type.versionPublisheden

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