Document Detail

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.
MedLine Citation:
PMID:  23348805     Owner:  NLM     Status:  MEDLINE    
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.
Kevin Colclough; Christine Bellanne-Chantelot; Cecile Saint-Martin; Sarah E Flanagan; Sian Ellard
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Publication Detail:
Type:  Journal Article     Date:  2013-04-02
Journal Detail:
Title:  Human mutation     Volume:  34     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-12     Completed Date:  2013-09-30     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  669-85     Citation Subset:  IM    
Copyright Information:
© 2013 Wiley Periodicals, Inc.
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MeSH Terms
Base Sequence
Chromosome Aberrations
CpG Islands
DNA Primers
Diabetes Mellitus, Type 2 / genetics*
Disease Models, Animal
Hepatocyte Nuclear Factor 1-alpha / genetics*
Hepatocyte Nuclear Factor 4 / genetics*
Hyperinsulinism / genetics*
Hypoglycemia / genetics*
Polymorphism, Genetic
Grant Support
098395//Wellcome Trust
Reg. No./Substance:
0/DNA Primers; 0/Hepatocyte Nuclear Factor 1-alpha; 0/Hepatocyte Nuclear Factor 4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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