Autosomal inheritance of diabetes in two families characterized by obesity and a novel H241Q mutation in NEUROD1

  1. Lucie Gonsorčíková1,
  2. Štěpánka Průhová1,2,
  3. Ondrej Cinek1,*,
  4. Jakob Ek3,4,
  5. Terezie Pelikánová5,
  6. Torben Jørgensen6,
  7. Hans Eiberg7,
  8. Oluf Pedersen3,8,
  9. Torben Hansen3,
  10. Jan Lebl1

Article first published online: 29 JUL 2008

DOI: 10.1111/j.1399-5448.2008.00379.x

Issue

Pediatric Diabetes

Pediatric Diabetes

Volume 9, Issue 4pt2, pages 367–372, August 2008

Additional Information

How to Cite

Gonsorčíková, L., Průhová, Š., Cinek, O., Ek, J., Pelikánová, T., Jørgensen, T., Eiberg, H., Pedersen, O., Hansen, T. and Lebl, J. (2008), Autosomal inheritance of diabetes in two families characterized by obesity and a novel H241Q mutation in NEUROD1. Pediatric Diabetes, 9: 367–372. doi: 10.1111/j.1399-5448.2008.00379.x

Author Information

  1. 1

    Department of Paediatrics, Second Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

  2. 2

    Department of Paediatrics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

  3. 3

    Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark

  4. 4

    Kennedy Center – The National Research Center for the Genetics of Visual Impairment and Mental Retardation, Glostrup, Denmark

  5. 5

    Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

  6. 6

    Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark

  7. 7

    Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark

  8. 8

    Faculty of Health Science, University of Aarhus, Aarhus, Denmark

*Ondrej Cinek, PhD Department of Paediatrics University Hospital Motol V Úvalu 84, CZ-150 06 Prague Czech Republic. Tel: +420 224 432 026; fax: +420 224 432 020; e-mail: ondrej.cinek@lfmotol.cuni.cz

Publication History

  1. Issue published online: 29 JUL 2008
  2. Article first published online: 29 JUL 2008
  3. Submitted 12 September 2007. Accepted for publication 20 December 2007

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Keywords:

  • maturity-onset diabetes of the young;
  • NEUROD1;
  • obesity

Background:  The aim of the study was to search for mutations in the NEUROD1 and IPF-1 genes in patients with clinical characteristics of maturity-onset diabetes of the young (MODY) but with no mutations in the HNF-4A (MODY1), GCK (MODY2) and TCF1 (MODY3) genes.

Methods:  We studied 30 unrelated Czech probands with a clinical diagnosis of MODY (median age at testing, 18 yr; median age at the recognition of hyperglycaemia, 16 yr). The promoter, exons and exon/intron boundaries of the NEUROD1 and IPF-1 genes were examined by polymerase chain reaction–denaturing high performance liquid chromatography and direct sequencing.

Results:  While no mutations were found in the IPF-1 gene, a novel H241Q substitution of NEUROD1 gene was identified in two unrelated families. In the first proband, the H241Q mutation led to early diagnosed (20 yr) hyperglycaemia followed by development of diabetic microvascular complications by the age of 32 yr. The second proband suffered from slowly progressing hyperglycaemia detected at the age of 30 yr. Affected members of both families were obese. The overall prevalence of the variant among the general population was 4 of 13 568 chromosomes.

Conclusions:  We report a novel disease-associated variant in NEUROD1 identified among a set of MODYX families. The variant seems to precipitate type-2-like diabetes in excessively obese individuals.

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