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http://purl.uniprot.org/citations/20546279http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Aims

Mutations in HNF4A cause a form of monogenic beta-cell diabetes. We aimed to identify mutations in the pancreas-specific P2 promoter of HNF4A in families with suspected HNF4A diabetes and to show that they impaired the function of the promoter in vitro.

Methods

We screened families with a clinical suspicion of HNF4A monogenic beta-cell diabetes for mutations in the HNF4A P2 promoter. We investigated the function of the previously reported HNF4A P2 promoter mutation -192C>G linked to late-onset diabetes in several families, along with two new segregating mutations, in vitro using a modified luciferase reporter assay system with enhanced sensitivity.

Results

We identified two novel HNF4A P2 promoter mutations that co-segregate with diabetes in two families, -136A>G and -169C>T. Both families displayed phenotypes typical of HNF4A monogenic beta-cell diabetes, including at least two affected generations, good response to sulphonylurea treatment and increased birthweight and/or neonatal hypoglycaemia. We show that both of these novel mutations and -192C>G impair the function of the promoter in transient transfection assays.

Conclusions

Two novel mutations identified here and the previously identified late-onset diabetes mutation, -192C>G, impair the function of the HNF4A P2 promoter in vitro."xsd:string
http://purl.uniprot.org/citations/20546279http://purl.org/dc/terms/identifier"doi:10.1111/j.1464-5491.2010.03003.x"xsd:string
http://purl.uniprot.org/citations/20546279http://purl.uniprot.org/core/author"Ellard S."xsd:string
http://purl.uniprot.org/citations/20546279http://purl.uniprot.org/core/author"Harries L.W."xsd:string
http://purl.uniprot.org/citations/20546279http://purl.uniprot.org/core/author"Gasperikova D."xsd:string
http://purl.uniprot.org/citations/20546279http://purl.uniprot.org/core/author"Klimes I."xsd:string
http://purl.uniprot.org/citations/20546279http://purl.uniprot.org/core/author"Stanik J."xsd:string
http://purl.uniprot.org/citations/20546279http://purl.uniprot.org/core/author"Ryffel G.U."xsd:string
http://purl.uniprot.org/citations/20546279http://purl.uniprot.org/core/author"Murphy R."xsd:string
http://purl.uniprot.org/citations/20546279http://purl.uniprot.org/core/author"Johnstone K.A."xsd:string
http://purl.uniprot.org/citations/20546279http://purl.uniprot.org/core/author"Wirsing A."xsd:string
http://purl.uniprot.org/citations/20546279http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20546279http://purl.uniprot.org/core/name"Diabet Med"xsd:string
http://purl.uniprot.org/citations/20546279http://purl.uniprot.org/core/pages"631-635"xsd:string
http://purl.uniprot.org/citations/20546279http://purl.uniprot.org/core/title"Novel monogenic diabetes mutations in the P2 promoter of the HNF4A gene are associated with impaired function in vitro."xsd:string
http://purl.uniprot.org/citations/20546279http://purl.uniprot.org/core/volume"27"xsd:string
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