Identification of eight novel glucokinase mutations in Italian children with maturity-onset diabetes of the young.
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.Ser433_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.
Mantovani
Vilma
V
Laboratorio Centralizzato Settore Genetica, Policlinico S.Orsola-Malpighi, Bologna, Italy. mantovan@med.unibo.it
Salardi
Silvana
S
Cerreta
Vincenzo
V
Bastia
Daniela
D
Cenci
Marinella
M
Ragni
Luca
L
Zucchini
Stefano
S
Parente
Raffaele
R
Cicognani
Alessandro
A
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000235:genetics*; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010641:Phenotype
D005941:Glucokinase