MODY type 2 P59S GCK mutant: Founder effect in South of Italy

M. Delvecchio, O. Ludovico, E. Bellacchio, R. Stallone, T. Palladino, S. Mastroianno, L. Zelante, M. Sacco, V. Trischitta, M. Carella

Research output: Contribution to journalArticle

Abstract

Mutations in the glucokinase (GCK) gene are the most frequent cause of maturity onset diabetes of the young (MODY) in Italy. We evaluated GCK mutations in 32 unrelated patients younger than 18 years who had been diagnosed with MODY. Eleven different GCK heterozygous mutations were identified in 22 (68.7%) of the 32 probands. Nine mutations were missense and two were nonsense. Three of these mutations (E17X, P59S and E372X) have not been described previously and were shown to be associated with hyperglycaemia. Several prediction methods suggested that the E17X and E372X mutations result in a premature truncated protein and that the P59S mutation is pathogenic. This idea was further supported by evidence suggesting that Proline 59 is a highly conserved amino acid residue and that the P59S mutation does not appear to be present in non-diabetic controls and in sequence variant databases. Furthermore, this mutation was found in six (27.3%) of the patients from the same geographical area, Gargano, pointing to the existence of a founder effect, which was confirmed by microsatellite analysis.

Original languageEnglish
Pages (from-to)83-87
Number of pages5
JournalClinical Genetics
Volume83
Issue number1
DOIs
Publication statusPublished - Jan 2013

Keywords

  • Diabetes
  • Founder effect
  • GCK-MODY
  • Genetics
  • Paediatrics

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Fingerprint Dive into the research topics of 'MODY type 2 P59S GCK mutant: Founder effect in South of Italy'. Together they form a unique fingerprint.

  • Cite this