Identification of eight new mutations in the GCK gene by DHPLC screening in a Spanish population.
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.
Solera
Jesús
J
Servicio de Bioquímica, Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, CIBERER, Madrid, Spain. jsolera.hulp@salud.madrid.org
Arias
Pedro
P
Amiñoso
Cintia
C
González-Casado
Isabel
I
Garre
Pilar
P
Herranz
Lucrecia
L
Villarroel
Africa
A
Cruz
Marta
M
Jáñez
Mercedes
M
Pallardo
Luís Felipe
LF
Gracia
Ricardo
R
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
D005941:Glucokinase