Genetic analysis of single-minded 1 gene in early-onset severely obese children and adolescents.

BACKGROUND: Inactivating mutations of the hypothalamic transcription factor singleminded1 (SIM1) have been shown as a cause of early-onset severe obesity. However, to date, the contribution of SIM1 mutations to the obesity phenotype has only been studied in a few populations. In this study, we screened the functional regions of SIM1 in severely obese children of Slovak and Moravian descent to determine if genetic variants within SIM1 may influence the development of obesity in these populations. METHODS: The SIM1 promoter region, exons and exon-intron boundaries were sequenced in 126 unrelated obese children and adolescents (2-18 years of age) and 41 adult lean controls of Slovak and Moravian origin. Inclusion criteria for the children and adolescents were a body mass index standard deviation score higher than 2 SD for an appropriate age and sex, and obesity onset at less than 5 years of age. The clinical phenotypes of the SIM1 variant carriers were compared with clinical phenotypes of 4 MC4R variant carriers and with 27 unrelated SIM1 and MC4R mutation negative obese controls that were matched for age and gender. RESULTS: Seven previously described SIM1 variants and one novel heterozygous variant p.D134N were identified. The novel variant was predicted to be pathogenic by 7 in silico software analyses and is located at a highly conserved position of the SIM1 protein. The p.D134N variant was found in an 18 year old female proband (BMI 44.2kg/m2; +7.5 SD), and in 3 obese family members. Regardless of early onset severe obesity, the proband and her brother (age 16 years) did not fulfill the criteria of metabolic syndrome. Moreover, the variant carriers had significantly lower preferences for high sugar (p = 0.02) and low fat, low carbohydrate, high protein (p = 0.02) foods compared to the obese controls. CONCLUSIONS: We have identified a novel SIM1 variant, p.D134N, in 4 obese individuals from a single pedigree which is also associated with lower preference for certain foods.

The results of interconnection of the evidence of professional exposure to genotoxic factors (regex) and cancer registry in the Czech Republic.

The aim of this study is to analyze the genotoxic risks in the Moravian-Silesian Region in the Czech Republic and assess the significance of genotoxic factors in the etiology of cancer by bringing together the Registry of Occupational Exposure to Genotoxic Factors and the Cancer Registry and compare the rate of detected cancer in persons exposed to genotoxic factors via their work in the Moravian-Silesian Region with the occurrence of cancer in the population of the Czech Republic. The results show: (a) For the monitored group (748 person) for the period 1996-2008, according to gender, was no statistically significant difference in the incidence of oncological diseases compared to the population of the Czech Republic. (b) But statistically significant difference was found in the cases of oncological diseases in groups according to % AB.C. using the Cytogenetic analysis of human peripheral lymphocytes (CAPL). The highest incidence was in the group with a higher incidence of % AB.C. High values of % AB.C. may predict the development of oncological diseases.