|
|
Genetics MODY diabetes
Dušátková, Petra ; Cinek, Ondřej (advisor) ; Haluzík, Martin (referee) ; Gašperíková, Daniela (referee)
The most common form of monogenic diabetes is MODY (Maturity-Onset Diabetes of the Young). It ranks among genetic defects of the β cell. It is clinically heterogenous group of disorders characterised with non insulin-dependent diabetes mellitus with autosomal dominant inheritance and age at diagnosis up to 40 years. We specified the diagnosis of MODY in more than 240 Czech families using molecular-genetic approach. The most common subtype of MODY is GCK-MODY which was proved in 376 subjects from 175 families. The risk of macrovascular complications in patiens with GCK-MODY was not detected. Additionally, we tested the ancestral origin of 4 recurrent mutations in the GCK gene causing GCK-MODY using genetic and statistical methods. We showed that three mutations (p.Glu40Lys, p.Leu315His, p.Gly318Arg) spread approximately 82-110 generations ago due to a founder effect. We also dealed with the impact of the rs560887 polymorphism on the phenotype of the patients with GCK-MODY. The genotype GG was associated with higher level of glycated haemoglobin. Analysis of patients suspect for HNF1A- or HNF4A-MODY revealed the probably first evidence of patient with HNF1A-MODY present with macrosomia and recurring ketotic hypoglycaemias in the childhood. The rare MODY genes were investigated in patients fulfilling the...
|
|
|
Genetic causes of MODY (Maturity-Onset Diabetes of the Young)- prevalence of mutations in the MODY genes in the Czech diabetic and nondiabetic populations
Lukášová, Petra ; Bendlová, Běla (advisor) ; Gašperíková, Daniela (referee) ; Mazura, Ivan (referee)
I I a I I I I I I I I I I I I I I I I I 6. CONCLUSTONS Theaimsof ourstudywereperformed. Twelvefamilieswithunrecognizedtypeof MODYwerecotlected. Quite largecohortsof DM2patients,direct offspringof DM2patients,gestational diabeticsandsufficienttylargegroupof controlsubjectswerecompleted.Attthe probands underwenta detaitedanthropometricand biochemicalcharacterisation.Datawere filled in anelectronicdatabase. TheDNAbankwasestablishedandcompleted. For GCK gene we adopted screeningmethodsSSCP for all exons specific for B-celts(1a-10)andTGGEfor exons1a-7andwe confirmedtheirhighsensitivityandthe 100%concordanceof both methods.Resultswere consequentlyconfirmedby direct sequencingin bothdirections. We founda novelheterozygousmissensemutationV33Aand a previoustypubtished mutationE40Kin exon2 of GCK genein two differnentCzechMODYfamilies.However, ourstudydid not providethe evidenceof GCK geneas a risk genein the pathogenesis of diabetesmellitustype2 or of the gestationaldiabetesin Czechpopulationbecausewe identifiedontyone intronicmutationin a gestationaldiabeticand no differencesin the frequenciesof GCKpolymorphismsbetweenCzechdiabeticandnondiabeticpopulations. We assessedthe frequencyof commonvariant-30G>Ain B-promoterof GCK gene. Atthoughwe did not detect the higherfrequencyof minor attele A in diabetic in...
|
|
|
Genetics MODY diabetes
Dušátková, Petra ; Cinek, Ondřej (advisor) ; Haluzík, Martin (referee) ; Gašperíková, Daniela (referee)
The most common form of monogenic diabetes is MODY (Maturity-Onset Diabetes of the Young). It ranks among genetic defects of the β cell. It is clinically heterogenous group of disorders characterised with non insulin-dependent diabetes mellitus with autosomal dominant inheritance and age at diagnosis up to 40 years. We specified the diagnosis of MODY in more than 240 Czech families using molecular-genetic approach. The most common subtype of MODY is GCK-MODY which was proved in 376 subjects from 175 families. The risk of macrovascular complications in patiens with GCK-MODY was not detected. Additionally, we tested the ancestral origin of 4 recurrent mutations in the GCK gene causing GCK-MODY using genetic and statistical methods. We showed that three mutations (p.Glu40Lys, p.Leu315His, p.Gly318Arg) spread approximately 82-110 generations ago due to a founder effect. We also dealed with the impact of the rs560887 polymorphism on the phenotype of the patients with GCK-MODY. The genotype GG was associated with higher level of glycated haemoglobin. Analysis of patients suspect for HNF1A- or HNF4A-MODY revealed the probably first evidence of patient with HNF1A-MODY present with macrosomia and recurring ketotic hypoglycaemias in the childhood. The rare MODY genes were investigated in patients fulfilling the...
|
guest ::
