Human Molecular Genetics, Vol 6, 583-586, Copyright © 1997 by Oxford University Press
M Vaxillaire, M Rouard, K Yamagata, N Oda, PJ Kaisaki, VV Boriraj, JC Chevre, V Boccio, RD Cox, GM Lathrop, P Dussoix, J Philippe, J Timsit, G Charpentier, G Velho, GI Bell and P Froguel
Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous
subtype of non-insulin-dependent diabetes mellitus (NIDDM) characterised by
early onset, autosomal dominant inheritance and a primary defect in insulin
secretion. Recent studies have shown that mutations in the two functionally
related transcription factors, hepatocyte nuclear factor 4 alpha
(HNF-4alpha) and hepatocyte nuclear factor 1 alpha (HNF-1alpha) are
associated with the MODY1 and MODY3 forms of diabetes respectively, whereas
mutations in the enzyme glucokinase are the cause of the MODY2 form. We
have examined 10 unrelated Caucasian families in which MODY/NIDDM
co-segregated with markers for MODY3 for mutations in the HNF-1alpha gene
(TCF1). Ten different mutations were observed in these families, all of
which co- segregated with diabetes. There were no obvious relationships
between the nature of the mutations observed (i.e. frameshift, nonsense, or
missense) or their location in the gene with clinical features of diabetes
(age at onset, severity) in these families. The mechanisms by which
mutations in the HNF-1alpha gene cause diabetes mellitus are unclear but
might include abnormal pancreatic islet development during foetal life
thereby limiting their later function, as well as impaired transcriptional
regulation of genes that play a key role in normal pancreatic beta cell
function.
ARTICLES
Identification of nine novel mutations in the hepatocyte nuclear factor 1 alpha gene associated with maturity-onset diabetes of the young (MODY3)
CNRS EP10, Institut Pasteur de Lille & CHU de Lille, France.
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