title: Identification of eight new mutations in the GCK gene by DHPLC screening in a Spanish population.
abstract: Maturity onset diabetes of the young (MODY) is a genetically heterogeneous disorder characterized by autosomal dominant inheritance, altered function of pancreatic beta cells and early onset diabetes mellitus, usually before 25 years old. The prevalence of specific mutations of MODY genes differs considerably among different countries. In this study we analyzed 53 index cases from unrelated MODY families who are potential carriers of mutations in GCK gene. In addition, 122 relatives were also studied. We have identified eight new mutations in the GCK gene. One of them is a non-frameshift deletion involving Lysine 143. This amino acid is part of the conserved stretch of basic residues (KHKKL) which spans from residue 140 to 144. The non-frameshift deletion might implicate the affinity of GCK for GCKRP, and potentially the abnormal nuclear localization of GCK. Additional studies should be performed to confirm this possibility.
authors.affiliation: Servicio de Bioquímica, Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, CIBERER, Madrid, Spain. jsolera.hulp@salud.madrid.org
authors.forename: Jesús
authors.initials: J
authors.lastname: Solera
authors.forename: Pedro
authors.initials: P
authors.lastname: Arias
authors.forename: Cintia
authors.initials: C
authors.lastname: Amiñoso
authors.forename: Isabel
authors.initials: I
authors.lastname: González-Casado
authors.forename: Pilar
authors.initials: P
authors.lastname: Garre
authors.forename: Lucrecia
authors.initials: L
authors.lastname: Herranz
authors.forename: Africa
authors.initials: A
authors.lastname: Villarroel
authors.forename: Marta
authors.initials: M
authors.lastname: Cruz
authors.forename: Mercedes
authors.initials: M
authors.lastname: Jáñez
authors.forename: Luís Felipe
authors.initials: LF
authors.lastname: Pallardo
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gracia
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001483:Base Sequence; D002675:Child, Preschool; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008322:Mammals / Q000235:genetics; D009154:Mutation; D016133:Polymerase Chain Reaction; D013030:Spain; D014982:Xenopus laevis / Q000235:genetics; D055815:Young Adult
chemical_list: D005941:Glucokinase