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Identification of eight novel glucokinase mutations in Italian children with maturity‐onset diabetes of the young
Author(s) -
Mantovani Vilma,
Salardi Silvana,
Cerreta Vincenzo,
Bastia Daniela,
Cenci Marinella,
Ragni Luca,
Zucchini Stefano,
Parente Raffaele,
Cicognani Alessandro
Publication year - 2003
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9179
Subject(s) - glucokinase , maturity onset diabetes of the young , exon , biology , missense mutation , genetics , nonsense mutation , mutation , population , gene , medicine , environmental health
Maturity‐onset diabetes of the young (MODY) is a clinically heterogeneous group of disorders characterized by early onset non‐insulin‐dependent diabetes mellitus, autosomal dominant inheritance, and primary defect in the function of the beta cells of the pancreas. Mutations in the glucokinase (GCK) gene account for 8%–56% of MODY, with the highest prevalences being found in the southern Europe. While screening for GCK mutations in 28 MODY families of Italian origin, we identified 17 different mutations (corresponding to 61% prevalence), including eight previously undescribed ones. The novel sequence variants included five missense mutations (p.Lys161Asn c.483G>C in exon 4, p.Phe171Leu c.511T>C in exon 5 and p.Thr228Ala c.682A>G, p.Thr228Arg c.683C>G, p.Gly258Cys c.772G>T in exon 7), one nonsense mutation (p.Ser383Ter c.1148C>A in exon 9), the splice site variant c.1253+1G>T in intron 9, and the deletion of 12 nucleotides in exon 10 (p.Ser433underscore;Ile436del c.1298_1309del12). Our study indicates that mutations in the GCK/MODY2 gene are a very common cause of MODY in the Italian population and broadens our knowledge of the naturally occurring GCK mutation repertoire. © 2003 Wiley‐Liss, Inc.