Browsing by Author "Todorovic, S. (55311644500)"

Purpose: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease characterized by impaired adrenal steroidogenesis and most often caused by CYP21A2 gene mutations. For the first time, we reported complete spectrum and frequency of CYP21A2 gene mutations in 61 unrelated patients with classical and non-classical CAH from Serbia. Methods: Direct DNA sequencing of whole CYP21A2 gene and polymerase chain reaction with sequence-specific primers for detection of CYP21A1P/CYP21A2 chimeras were combined. Results: We identified 18 different pathogenic alleles - two of them novel. Mutation detection rate was highest in patients with salt-wasting form of CAH (94.7 %). The most prevalent mutation was intron 2 splice site mutation, c.290-13A/C>G (18.5 %). Other mutation frequencies were: CYP21A1P/CYP21A2 chimeras (13 %), p.P30L (13 %), p.R356W (11.1 %), p.G110fs (7.4 %), p.Q318X (4.6 %), p.V281L (4.6 %), p.I172N (2.8 %), p.L307fs (2.8 %), p.P453S (1.9 %), etc. Mainly, frequencies were similar to those in Slavic populations and bordering countries. However, we found 6.5 % of alleles with multiple mutations, frequently including p.P453S. Effects of novel mutations, c.386T>C (p.Leu129Pro) and c.493T>C (p.Ser165Pro), were characterized in silico as deleterious. The effect of well-known mutations on Serbian patients' phenotype was as expected. Conclusions: The first comprehensive molecular genetic study of Serbian CAH patients revealed two novel CYP21A2 mutations. This study will enable genetic counseling in our population and contribute to better understanding of molecular landscape of CAH in Europe. © 2015 Italian Society of Endocrinology (SIE).

Purpose: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease characterized by impaired adrenal steroidogenesis and most often caused by CYP21A2 gene mutations. For the first time, we reported complete spectrum and frequency of CYP21A2 gene mutations in 61 unrelated patients with classical and non-classical CAH from Serbia. Methods: Direct DNA sequencing of whole CYP21A2 gene and polymerase chain reaction with sequence-specific primers for detection of CYP21A1P/CYP21A2 chimeras were combined. Results: We identified 18 different pathogenic alleles - two of them novel. Mutation detection rate was highest in patients with salt-wasting form of CAH (94.7 %). The most prevalent mutation was intron 2 splice site mutation, c.290-13A/C>G (18.5 %). Other mutation frequencies were: CYP21A1P/CYP21A2 chimeras (13 %), p.P30L (13 %), p.R356W (11.1 %), p.G110fs (7.4 %), p.Q318X (4.6 %), p.V281L (4.6 %), p.I172N (2.8 %), p.L307fs (2.8 %), p.P453S (1.9 %), etc. Mainly, frequencies were similar to those in Slavic populations and bordering countries. However, we found 6.5 % of alleles with multiple mutations, frequently including p.P453S. Effects of novel mutations, c.386T>C (p.Leu129Pro) and c.493T>C (p.Ser165Pro), were characterized in silico as deleterious. The effect of well-known mutations on Serbian patients' phenotype was as expected. Conclusions: The first comprehensive molecular genetic study of Serbian CAH patients revealed two novel CYP21A2 mutations. This study will enable genetic counseling in our population and contribute to better understanding of molecular landscape of CAH in Europe. © 2015 Italian Society of Endocrinology (SIE).

An increase in the prevalence of pediatric type 2 diabetes mellitus (T2DM) has been reported by numerous studies in the United States during the past two decades. Available data from Europe are scarce, but also suggest the rising prevalence of this disease in overweight children. The aim of this study was to determine the prevalence of previously undiagnosed T2DM, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in a clinic cohort of otherwise healthy overweight and obese Caucasian children and adolescents living in Serbia. The study group consisted of 301 subjects (176 girls, 125 boys) aged 5.218.9 years, with body mass index >90th percentile. Oral glucose tolerance test was performed in all subjects. Previously undiagnosed T2DM was discovered in 0.3% (n1) and impaired glucose regulation in 15.9% (n48) of the subjects. Isolated IFG was detected in 4.3% (n13), isolated IGT in 8.3% (n25) and combined IFG and IGT in 3.3% (n10) of the subjects. Disturbances of glucose metabolism were present in a substantial number of the subjects, which emphasizes the need for prevention and treatment of childhood obesity. © 2012 Macmillan Publishers Limited.

An increase in the prevalence of pediatric type 2 diabetes mellitus (T2DM) has been reported by numerous studies in the United States during the past two decades. Available data from Europe are scarce, but also suggest the rising prevalence of this disease in overweight children. The aim of this study was to determine the prevalence of previously undiagnosed T2DM, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in a clinic cohort of otherwise healthy overweight and obese Caucasian children and adolescents living in Serbia. The study group consisted of 301 subjects (176 girls, 125 boys) aged 5.218.9 years, with body mass index >90th percentile. Oral glucose tolerance test was performed in all subjects. Previously undiagnosed T2DM was discovered in 0.3% (n1) and impaired glucose regulation in 15.9% (n48) of the subjects. Isolated IFG was detected in 4.3% (n13), isolated IGT in 8.3% (n25) and combined IFG and IGT in 3.3% (n10) of the subjects. Disturbances of glucose metabolism were present in a substantial number of the subjects, which emphasizes the need for prevention and treatment of childhood obesity. © 2012 Macmillan Publishers Limited.