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| Articles
by
I. Klimes |
Total Records (
1 ) for
I. Klimes |
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A. Wirsing
,
K. A. Johnstone
,
L. W. Harries
,
S. Ellard
,
G. U. Ryffel
,
J. Stanik
,
D. Gasperikova
,
I. Klimes
and
R. Murphy
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Aims Mutations in HNF4A cause a form of monogenic β-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 β-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 β-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. |
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