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Exp Clin Endocrinol Diabetes 2012; 120(02): 89-90
DOI: 10.1055/s-0031-1284378
Article
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Monogenic Diabetes in a Family with 2 unknown HNF-4A Gene Mutations

M. Motzkau
1   Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University of Magdeburg, Germany
,
P. Meyer
2   Institute of Molecular Medicine, Munich, Germany
,
P.R. Mertens
1   Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University of Magdeburg, Germany
,
S. Klose
1   Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University of Magdeburg, Germany
› Author Affiliations
Further Information

Publication History

received 30 May 2011
firstdecision 30 May 2011

accepted 13 July 2011

Publication Date:
15 September 2011 (online)

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Abstract

Introduction:

Diabetes mellitus classified as Maturity Onset Diabetes of the Young (MODY) is characterized by autosomal dominant inheritance with insulin secretory disturbances.

Case report:

In 2 siblings with diabetes mellitus manifestation at age under 25 years, low fasting glucose levels, severely elevated glucose levels upon glucose challenge and absent autoantibodies for IA2 and GAD clarification for MODY was sought. Mutational screening for MODY 1–3 mutations was carried out by direct sequencing followed by multiplex ligation-dependent probe amplification (MLPA).

Conclusion:

We identified a mutation within the hepatic nuclear factor 4A (HNF-4A) gene hitherto unreported for MODY-1. A causative role of the mutation is not proven, however in the 2 index patients similar phenotypes are present. These cases underline the necessity to screen for MODY when the medical history and lack of autoantibodies suggest alternative diagnoses beside type 1 diabetes.

Key words

diabetes - Maturity Onset Diabetes of the Young - insulin secretory disturbances - hepatic nuclear factor 4A
 

  • References

  • 1 Gat-Yablonski G, Shalitin S, Phillip M. Maturity onset diabetes of the young-review. Pediatr Endocrinol 2006; 3 (Suppl 3) 514-520
    PubMedGoogle Scholar
  • 2 Ellard S, Bellanné-Chantelot C, Hattersley AT. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia 2008; 51 (04) 546-553
    CrossrefPubMedGoogle Scholar
  • 3 Borowiec M, Liew CW, Thompson R et al. Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc Nat Acad Sci 2009; 106: 14460-14465
    CrossrefPubMedGoogle Scholar
  • 4 Kim SH, Ma X, Weremowicz S et al. Identification of a locus for maturity-onset diabetes of the young on chromosome 8p23. Diabetes 2004; 53: 1375-1384
    CrossrefPubMedGoogle Scholar
  • 5 Love-Gregory L, Permutt MA. HNF4A genetic variants: role in diabetes. Curr Opin Clin Nutr Metab Care 2007; 10 (04) 397-402
    CrossrefPubMedGoogle Scholar
  • 6 Pearson ER, Pruhova S, Tack CJ et al. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection. Diabetologia 2005; 48 (05) 878-885
    CrossrefPubMedGoogle Scholar
  • 7 Pruhova S, Ek J, Lebl J et al. Genetic epidemiology of MODY in the Czech republic: new mutations in the MODY genes HNF-4alpha, GCK and HNF-1alpha. Diabetologia 2003; 46 (02) 291-295
    PubMedGoogle Scholar
  • 8 Taghavi SM, Fatemi SS, Rafatpanah H et al. Mutations in the coding regions of the hepatocyte nuclear factor 4 alpha in Iranian families with maturity onset diabetes of the young. Cardiovasc Diabetol 2009; 10;8: 63
    PubMedGoogle Scholar
  • 9 Hara K, Noda M, Waki H et al. Maturity-onset diabetes of the young resulting from a novel mutation in the HNF-4alpha gene. Intern Med 2002; 41 (10) 848-852
    CrossrefPubMedGoogle Scholar