Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis.

OBJECTIVE: To evaluate the candidate genes PAX-8, NKX2-5, TSH-R and HES-1 in 63 confirmed cases of thyroid dysgenesis. SUBJECTS AND METHODS: Characterization of patients with congenital hypothyroidism into specific subtypes of thyroid dysgenesis with hormone levels (TT4 and TSH), thyroid ultrasound and scintigraphy. DNA was extracted from peripheral blood leukocytes and the genetic analysis was realized by investigating the presence of mutations in the transcription factor genes involved in thyroid development. RESULTS: No mutations were detected in any of the candidate genes. In situ thyroid gland represented 71.1% of all cases of permanent primary congenital hypothyroidism, followed by hypoplasia (9.6%), ectopia (78%), hemiagenesis (6.0%) and agenesis (5.5%). The highest neonatal screening TSH levels were in the agenesis group (p < 0.001). CONCLUSIONS: Thyroid dysgenesis is possibly a polygenic disorder and epigenetic factors could to be implicated in these pathogeneses.

Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis

ABSTRACT Objective: To evaluate the candidate genes PAX-8, NKX2-5, TSH-R and HES-1 in 63 confirmed cases of thyroid dysgenesis. Subjects and methods: Characterization of patients with congenital hypothyroidism into specific subtypes of thyroid dysgenesis with hormone levels (TT4 and TSH), thyroid ultrasound and scintigraphy. DNA was extracted from peripheral blood leukocytes and the genetic analysis was realized by investigating the presence of mutations in the transcription factor genes involved in thyroid development. Results: No mutations were detected in any of the candidate genes. In situ thyroid gland represented 71.1% of all cases of permanent primary congenital hypothyroidism, followed by hypoplasia (9.6%), ectopia (78%), hemiagenesis (6.0%) and agenesis (5.5%). The highest neonatal screening TSH levels were in the agenesis group (p < 0.001). Conclusions: Thyroid dysgenesis is possibly a polygenic disorder and epigenetic factors could to be implicated in these pathogeneses.

HLA class II polymorphism in patients with type 1 diabetes mellitus from a Brazilian racially admixtured population.

BACKGROUND: Several studies have demonstrated a fundamental role for the histocompatibility antigens (ie, human leukocyte antigens or HLA) in the susceptibility of, or protection to, type 1 diabetes mellitus (T1DM). However, this has not been adequately studied in racially admixtured populations. OBJECTIVES: To assess the frequency of HLA class II (DQA1, DQB1 and DRB1) associated to susceptibility or protection toT1DM in a Brazilian racially admixtured with diabetes. METHODS: Cross-sectional study. The HLA genotyping was performed by a polymerase chain reaction hybridization assay. The racial groups were categorized by self-report and phenotype. The results are expressed as means and standard deviations of the mean, proportions and frequencies. The chi2 and Fisher exact tests were used for the inferential statistics. RESULTS: The study population comprised 55 children and adolescents with T1DM. The phenotypic racial group classification demonstrated that, 60% were Mulattoes, 25.5% Whites, 12.7% Blacks and 1.8% from Indian ancestry. The T1DM's susceptibility was associated with an increased frequency of the HLA of risk (-DRB1*0401, -DRB1*0402, DQA1*03, -DQA1*05, -DQB1*02 e -DQB1*0302); and a small frequency of protective alleles (-DRB1*0404, -DRB1*0407, -DQA1*0201, -DQB1*0602, -DQB*0603 e -DQB1*0604) in all subjects. We found a greater frequency of the HLA-DRB1*0302 among Whites when compared to Blacks. CONCLUSIONS: This study demonstrates that the frequency and distribution of the susceptibility and protective HLA alleles were similar to studies performed in the Brazilian Southeast and in North Americans and European Caucasians, suggesting that the genetic basis of T1DM has a common origin being little modified by racial characteristics.

Poor zinc and selenium status in phenylketonuric children and adolescents in Brazil.

Because of the restricted intake of high-biologic-value protein, children with phenylketonuria (PKU) may have lower than normal plasma concentrations of copper, zinc, and selenium. The purpose of the present study was to investigate erythrocyte zinc levels and serum copper and selenium levels in children and adolescents with PKU by analyzing the relation between their diet and the laboratory profiles of these elements. The study was conducted in 32 children and adolescents with PKU, who were on a special diet. Dietary records and blood samples were collected from each subject. Erythrocyte zinc and serum selenium levels were below normal in 37.5% and 90.6% of the subjects, respectively. Plasma copper levels were normal. Metabolic formulas were the only source of 86.9% of the zinc, 65.6% of the copper, and 32.4% of the selenium. Despite this, there was no significant correlation between the zinc formula supply and erythrocyte zinc levels (rho = -0.143, P = .435) or the supply and serum levels for copper (rho = -0.117, P = .523) and selenium (rho = 0.113, P = .538). These results suggest that Brazilian patients with PKU present with low ingestion levels, low serum selenium levels, and low erythrocyte zinc levels.