Diabetologia

, Volume 40, Issue 2, pp 217–224

Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families

  • G. Velho
  • H. Blanché
  • M. Vaxillaire
  • C. Bellanné-Chantelot
  • V. C. Pardini
  • J. Timsit
  • P. Passa
  • I. Deschamps
  • J.-J. Robert
  • I. T. Weber
  • D. Marotta
  • S. J. Pilkis
  • G. M. Lipkind
  • G. I. Bell
  • P. Froguel

DOI: 10.1007/s001250050666

Cite this article as:
Velho, G., Blanché, H., Vaxillaire, M. et al. Diabetologia (1997) 40: 217. doi:10.1007/s001250050666

Summary

Mutations in glucokinase are associated with defects in insulin secretion and hepatic glycogen synthesis resulting in mild chronic hyperglycaemia, impaired glucose tolerance or diabetes mellitus. We screened members of 35 families with features of maturity-onset diabetes of the young for mutations in the glucokinase gene and found 16 different mutations. They included 14 new mutations in the glucokinase gene: 9 missense mutations (A53S, G80A, H137R, T168P, M210T, C213R, V226M, S336L and V367M); 2 nonsense mutations (E248X and S360X); a deletion of one nucleotide resulting in a frameshift (V401del1); a substitution of a conserved nucleotide at a splice acceptor site (L122-1G → T); and a 10 base pair deletion that removed the GT of the splice donor site and the following eight nucleotides (K161 + 2del10). In addition, we found two previously identified mutations: R186X and G261R. Study of 260 subjects with glucokinase-deficient hyperglycaemia from 42 families with 36 different GCK mutations made it possible to define the clinical profile of this subtype of non-insulin-dependent diabetes mellitus (NIDDM). Hyperglycaemia due to glucokinase deficiency is often mild (fewer than 50 % of subjects have overt diabetes) and is evident during the early years of life. Despite the long duration of hyperglycaemia, glucokinase-deficient subjects have a low prevalence of micro- and macro-vascular complications of diabetes. Obesity, arterial hypertension and dyslipidaemia are also uncommon in this form of NIDDM. [Diabetologia (1997) 40: 217–224]

Keywords Diabetes mellitus MODY glucokinase mutations insulin secretion genetics. 

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • G. Velho
    • 1
  • H. Blanché
    • 2
  • M. Vaxillaire
    • 3
  • C. Bellanné-Chantelot
    • 2
  • V. C. Pardini
    • 4
  • J. Timsit
    • 5
  • P. Passa
    • 6
  • I. Deschamps
    • 7
  • J.-J. Robert
    • 7
  • I. T. Weber
    • 8
  • D. Marotta
    • 9
  • S. J. Pilkis
    • 9
  • G. M. Lipkind
    • 10
  • G. I. Bell
    • 10
  • P. Froguel
    • 3
  1. 1.INSERM U-358, Hôpital Saint Louis, Paris, FranceFR
  2. 2.Fondation Jean Dausset-CEPH, Paris, FranceFR
  3. 3.CNRS EP-10, Institut Pasteur et CHU de Lille, Lille, FranceFR
  4. 4.CEPEN, Belo Horizonte, MG, BrazilBR
  5. 5.Service d'Immunologie Clinique, Hôpital Necker-Enfants Malades, Paris, FranceFR
  6. 6.Service d'Endocrinologie et Diabétologie, Hôpital Saint Louis, Paris, FranceFR
  7. 7.INSERM U-30, Hôpital Necker-Enfants Malades, Paris, FranceFR
  8. 8.Department of Pharmacology, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania, USAUS
  9. 9.Department of Biochemistry, University of Minnesota, Minneapolis, Minnesota, USAUS
  10. 10.Howard Hughes Medical Institute and Departments of Biochemistry and Molecular Biology and Medicine, The University of Chicago, Chicago, IllinoisXX

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