Alexis Dourado Guedes

Detection of Hidden Y Mosaicism in Turner's Syndrome: Importance in the Prevention of Gonadoblastoma

UNLABELLED The presence of Y chromosome fragments in patients with Turners syndrome (TS) is known to increase the risk of gonadoblastoma. The investigation of Y sequences is usually performed only in the presence of marker chromosomes and therefore does not rule out the presence of hidden mosaicism in patients with 45,X TS without any marker. AIMS 1. To investigate the presence of hidden Y mosaicism in non-mosaic 45,X patients with TS, using samples from different tissues, and its association with the development of gonadoblastoma. STUDY DESIGN Twenty patients with a 45,X karyotype were studied. The SRY and DYZ3 sequences were amplified by PCR, using genomic DNA from peripheral blood, oral epithelial cells and hair roots. Prophylactic gonadectomy was offered to the Y-positive patients. RESULTS The analysis of the different tissues revealed that seven (35%) out of the 20 patients studied presented hidden chromosome Y mosaicism. Four of these patients underwent prophylactic gonadectomy, and bilateral gonadoblastoma was found in one of them. CONCLUSIONS A systematic search for hidden Y chromosome mosaicism in patients with TS and 45,X karyotype is justified by the possibility of developing gonadoblastoma.

Y chromosome in Turner syndrome: review of the literature

Turner syndrome (TS) is one of the most common types of aneuploidy among humans, and is present in 1:2000 newborns with female phenotype. Cytogenetically, the syndrome is characterized by sex chromosome monosomy (45,X), which is present in 50-60% of the cases. The other cases present mosaicism, with a 45,X cell line accompanied by one or more other cell lines with a complete or structurally abnormal X or Y chromosome. The presence of Y-chromosome material in patients with dysgenetic gonads increases the risk of gonadal tumors, especially gonadoblastoma. The greatest concern is the high risk of developing gonadoblastoma or other tumors and virilization during puberty if chromosome Y-specific sequences are present. The role of the Y chromosome in human oncogenesis is still controversial. Even though gonadoblastoma is a benign tumor, it can undergo transformation into invasive dysgerminoma in 60% of the cases, and also into other, malignant forms of germ cell tumors. Although some authors have questioned the high incidence of gonadoblastoma (around 30%), the risk of developing any kind of gonadal lesion, whether tumoral or not, justifies investigation of Y-chromosome sequences by means of the polymerase chain reaction (PCR), a highly sensitive, low-cost and easy-to-perform technique. In conclusion, mosaicism of both the X and the Y chromosome is a common finding in TS, and detection of Y-chromosome-specific sequences in patients, regardless of their karyotype, is necessary in order to prevent the development of gonadal lesions.

A obesidade e sua associação com os demais fatores de risco cardiovascular em escolares de Itapetininga, Brasil

FUNDAMENTO: A escassez de dados sobre a obesidade infantil e o risco cardiovascular no Brasil. OBJETIVO: Determinar a prevalencia de hipertensao, dislipidemia, obesidade e suas correlacoes em uma amostra de escolares de Itapetininga-SP. METODOS: Corte transversal com coleta sistematizada de dados antropometricos (peso, altura, cintura, indice de massa corporal e niveis pressoricos) e dosagens de glicose, colesterol (total e fracoes), acido urico e apolipoproteina A e B, em uma amostra aleatoria, representativa de escolares da rede publica de Itapetininga-SP. Analise dos dados utilizando parâmetros populacionais das curvas do NCHS(2000), categorias de pressao arterial do NHBPEP(2004) e categorias dos niveis sericos de colesterol propostos pela AHA para criancas e adolescentes(2003). RESULTADOS: Um total de 494 criancas e adolescentes participaram do estudo. Dos participantes, 11,7% apresentaram HAS, 51% apresentaram aumento do colesterol total, 40,5% apresentaram aumento do LDL-colesterol, 8,5% apresentaram aumento dos triglicerides e 6,1% tiveram valores baixos de HDL-colesterol. As medias (±desvio padrao) do CT, HDL-colesterol, LDL-colesterol e triglicerides foram respectivamente 172,1(27,9), 48,1(10,0), 105,7(23,1) e 90,9(43,8). A obesidade e o sobrepeso foram detectados em 12,8% e 9,7% da amostra, sendo que a obesidade determinou uma maior chance de se detectar a dislipidemia e a hipertensao quando comparada com os demais grupos. CONCLUSAO: Este estudo fornece subsidios para a hipotese de uma distinta prevalencia de excesso de peso entre escolares da rede publica das regioes nordeste e sudeste, maior nesta ultima. Adicionalmente, demonstra uma associacao da obesidade com a dislipidemia e a hipertensao naquele grupo. Diante da incipiencia de dados no Brasil sobre a questao estudada, o nosso trabalho fornece dados importantes para futuras comparacoes.BACKGROUND Paucity of data on childhood obesity and cardiovascular risk in Brazil. OBJECTIVE To determine the prevalence of hypertension, dyslipidemia, obesity and their correlations in a sample of school children in Itapetininga, State of Sao Paulo, Brazil. METHODS Cross-sectional study with systematic collection of anthropometric data (weight, height, waist circumference, BMI and blood pressure levels) and determination of glucose, total cholesterol, LDL, HDL, uric acid, and apolipoproteins A and B in a random sample representative of school children from the public education system in Itapetininga, State of Sao Paulo. For data analysis, we used population parameters from the NCHS curves (2000), blood pressure categories from NHBPEP (2004), and the serum cholesterol levels proposed by the AHA for children and adolescents (2003). RESULTS A total of 494 children and adolescents participated in the study. Of these, 11.7% had HBP, 51% increased total cholesterol, 40.5% increased LDL-cholesterol, 8.5% increased triglycerides, and 6.1% low HDL-cholesterol levels. Mean (+/- standard deviation) TC, HDL-cholesterol, LDL-cholesterol and triglycerides were 172.1(27.9), 48.1(10.0), 105.7(23.1) and 90.9(43.8), respectively. Obesity and overweight were detected in 12.8% and 9.7% of the sample, respectively. Individuals of the obese group had a greater chance of presenting with dyslipidemia and hypertension in comparison with those of the other groups. CONCLUSION This study supports the hypothesis of different prevalences of excess weight among school children from the public education system of the northeastern and southeastern regions of Brazil, with higher rates in the latter. Additionally, it demonstrates an association of obesity with dyslipidemia and hypertension in that group. In light of the paucity of Brazilian data on this issue, our study provides important data for further comparisons.

Prevalence of the polymorphism MTHFR A1298C and not MTHFR C677T is related to chromosomal aneuploidy in Brazilian Turner Syndrome patients

BACKGROUND Dysfunctions in the folate metabolism can result in DNA hypomethylation and abnormal chromosome segregation. Two common polymorphisms of this enzyme (C677T and A1298C) reduce its activity, but when associated with aneuploidy studies the results are conflicting. The objective of the present study is to analyze the MTHFR gene polymorphisms in women with Turner Syndrome and in a control group, correlating the findings to the chromosomal aneuploidy. METHODS The study comprised 140 patients with Turner Syndrome, of which 36 with chromosome mosaicism and 104 non-mosaics, and a control group of 209 fertile and healthy women without a history of any offspring with aneuploidy. Polymorphisms C677T and A1298C were studied by RFLP-PCR and the results were statistically analyzed. RESULTS The frequency of genotypes MTHFR 677CC, 677CT and 677TT in the patients with Turner Syndrome and chromosome mosaicism was, respectively, 58.3%, 38.9% and 2.8%. Among the patients with non-mosaic Turner Syndrome, 47.1% presented genotype 677CC, 45.2% genotype 677CT, and 7.7% genotype 677TT. Among the 209 individuals of the control group, genotypes 677CC, 677CT and 677TT were found at the following frequencies: 48.3%, 42.1% and 9.6%, respectively. As for polymorphism A1298C, the patients with Turner Syndrome and chromosome mosaicism presented genotypes 1298AA, 1298AC and 1298CC at the following frequencies: 58.3%, 27.8% and 13.9%, respectively. Among the non-mosaic Turner Syndrome patients, genotype 1298AA was found in 36.5%, genotype 1298AC in 39.4%, and genotype 1298CC in 22.1%. In the control group, genotypes 1298AA, 1298AC and 1298CC were present at the following frequencies: 52.6%, 40.7% and 6.7%, respectively. CONCLUSION No correlation was observed between the MTHFR gene polymorphism 677 and chromosomal aneuploidy in the Turner Syndrome patients. However, the MTHFR gene polymorphism at position 1298, mainly genotype 1298CC that reduces the enzyme efficiency, was more frequent in the group of Turner Syndrome patients, suggesting its involvement in mechanisms related to chromosomal imbalances.

PTPN22 C1858T Polymorphism in Women with Endometriosis

Citation Gomes FMCS, Bianco B, Teles JS, Christofolini DM, de Souza AMB, Guedes AD, Barbosa CP. PTPN22 C1858T polymorphismin women with endometriosis. Am J Reprod Immunol 2010; 63: 227–232

Clinical implications of the detection of Y-chromosome mosaicism in Turner's syndrome: report of 3 cases

OBJECTIVE To determine the clinical implications of the presence of a Y chromosome in Turners syndrome patients with karyotype abnormalities. DESIGN To investigate the presence of Y-chromosome sequences in different tissue samples. SETTING Endocrinology outpatient clinic of a federal university in Brazil. PATIENT(S) Five Turners syndrome patients with karyotype abnormalities such as marker chromosomes, additional material, or ring chromosomes. INTERVENTION(S) Peripheral blood, oral epithelial cells, and hair root samples were collected. MAIN OUTCOME MEASURE(S) The SRY gene and the DYZ3 repeat region were amplified by polymerase chain reaction followed by gel electrophoresis mobility of amplified genomic DNA, and ultraviolet visualization. Prophylactic gonadectomy was offered to the Y-positive patients. RESULT(S) The analysis of the different tissues revealed that three of the five patients studied presented Y-chromosome mosaicism. These three patients underwent prophylactic gonadectomy, and in one of them, the histopathologic study of the gonads disclosed hilus cell hyperplasia and stromal luteoma with contralateral nodular hyperthecosis. CONCLUSION(S) A systematic search for Y-chromosome mosaicism in Turners syndrome patients is justified by the risk of developing gonadal tumors or androgen-producing lesions.

Endogenous oestradiol but not testosterone is related to coronary artery disease in men

Objectives  Men die of coronary artery disease (CAD) more often than women. There is evidence that testosterone either is neutral or has a beneficial effect on male cardiovascular disease. The role of oestrogens in male CAD has been less studied. This study was carried out with the purpose of evaluating the relationship between sex hormone levels and CAD.

Determination of the sexual phenotype in a child with 45,X/46,X,Idic(Yp) mosaicism: Importance of the relative proportion of the 45,X line in gonadal tissue†

We report on a girl who, despite her 45,X/46,X,der(Y) karyotype, showed no signs of virilization or physical signs of the Ullrich–Turner syndrome (UTS), except for a reduced growth rate. After prophylactic gonadectomy due to the risk of developing gonadoblastoma, the gonads and peripheral blood samples were analyzed by fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) to detect Y‐specific sequences. These analyses allowed us to characterize the Y‐derived chromosome as being an isodicentric Yp chromosome (idic(Yp)) and showed a pronounced difference in the distribution of the 45,X/46,X,idic(Yp) mosaicism between the two analyzed tissues. It was shown that, although in peripheral blood almost all cells (97.5%) belonged to the idic(Yp) line with a duplicated SRY gene, this did not determine any degree of male sexual differentiation in the patient, as in the gonads the predominant cell line was 45,X (60%).

Obesity and its association with other cardiovascular risk factors in school children in Itapetininga, Brazil

FUNDAMENTO: A escassez de dados sobre a obesidade infantil e o risco cardiovascular no Brasil. OBJETIVO: Determinar a prevalencia de hipertensao, dislipidemia, obesidade e suas correlacoes em uma amostra de escolares de Itapetininga-SP. METODOS: Corte transversal com coleta sistematizada de dados antropometricos (peso, altura, cintura, indice de massa corporal e niveis pressoricos) e dosagens de glicose, colesterol (total e fracoes), acido urico e apolipoproteina A e B, em uma amostra aleatoria, representativa de escolares da rede publica de Itapetininga-SP. Analise dos dados utilizando parâmetros populacionais das curvas do NCHS(2000), categorias de pressao arterial do NHBPEP(2004) e categorias dos niveis sericos de colesterol propostos pela AHA para criancas e adolescentes(2003). RESULTADOS: Um total de 494 criancas e adolescentes participaram do estudo. Dos participantes, 11,7% apresentaram HAS, 51% apresentaram aumento do colesterol total, 40,5% apresentaram aumento do LDL-colesterol, 8,5% apresentaram aumento dos triglicerides e 6,1% tiveram valores baixos de HDL-colesterol. As medias (±desvio padrao) do CT, HDL-colesterol, LDL-colesterol e triglicerides foram respectivamente 172,1(27,9), 48,1(10,0), 105,7(23,1) e 90,9(43,8). A obesidade e o sobrepeso foram detectados em 12,8% e 9,7% da amostra, sendo que a obesidade determinou uma maior chance de se detectar a dislipidemia e a hipertensao quando comparada com os demais grupos. CONCLUSAO: Este estudo fornece subsidios para a hipotese de uma distinta prevalencia de excesso de peso entre escolares da rede publica das regioes nordeste e sudeste, maior nesta ultima. Adicionalmente, demonstra uma associacao da obesidade com a dislipidemia e a hipertensao naquele grupo. Diante da incipiencia de dados no Brasil sobre a questao estudada, o nosso trabalho fornece dados importantes para futuras comparacoes.BACKGROUND Paucity of data on childhood obesity and cardiovascular risk in Brazil. OBJECTIVE To determine the prevalence of hypertension, dyslipidemia, obesity and their correlations in a sample of school children in Itapetininga, State of Sao Paulo, Brazil. METHODS Cross-sectional study with systematic collection of anthropometric data (weight, height, waist circumference, BMI and blood pressure levels) and determination of glucose, total cholesterol, LDL, HDL, uric acid, and apolipoproteins A and B in a random sample representative of school children from the public education system in Itapetininga, State of Sao Paulo. For data analysis, we used population parameters from the NCHS curves (2000), blood pressure categories from NHBPEP (2004), and the serum cholesterol levels proposed by the AHA for children and adolescents (2003). RESULTS A total of 494 children and adolescents participated in the study. Of these, 11.7% had HBP, 51% increased total cholesterol, 40.5% increased LDL-cholesterol, 8.5% increased triglycerides, and 6.1% low HDL-cholesterol levels. Mean (+/- standard deviation) TC, HDL-cholesterol, LDL-cholesterol and triglycerides were 172.1(27.9), 48.1(10.0), 105.7(23.1) and 90.9(43.8), respectively. Obesity and overweight were detected in 12.8% and 9.7% of the sample, respectively. Individuals of the obese group had a greater chance of presenting with dyslipidemia and hypertension in comparison with those of the other groups. CONCLUSION This study supports the hypothesis of different prevalences of excess weight among school children from the public education system of the northeastern and southeastern regions of Brazil, with higher rates in the latter. Additionally, it demonstrates an association of obesity with dyslipidemia and hypertension in that group. In light of the paucity of Brazilian data on this issue, our study provides important data for further comparisons.

PTPN22 Polymorphism is Related to Autoimmune Disease Risk in Patients with Turner Syndrome

Individuals with Turner syndrome (TS) clearly have an increased risk for autoimmune diseases. Recently, an allelic variation (C1858T) of the PTPN22 gene was revealed to be associated with the development of autoimmunity. Thus, the aim of this study was to determine the frequency of the PTPN22 C1858T polymorphism in women with Turner syndrome (TS) compared to controls. Case–control study comprises 142 women with TS (cases) and 180 healthy and fertile women without a history of autoimmune disease (controls). Detection of the PTPN22 C1858T polymorphism (rs2476601) was performed by TaqMan real‐time PCR. The chi‐square test was used to compare allele and genotype frequencies between groups and to estimate the Hardy–Weinberg equilibrium. All P‐values were two‐tailed, and 95% confidence intervals (CIs) were calculated. A P‐value <0.05 was considered statistically significant. Genotypes CC, CT and TT of the PTPN22 C1858T polymorphism presented frequencies of, respectively, 67.6%, 28.2% and 4.2% in the TS, and 82.8%, 16.1% and 1.1% in the control group (P = 0.0043). Alleles C and T were present in, respectively, 81.7% and 18.3% of the patients with TS (P = 0.001, OR = 2.22, 95% CI = 1.39‐3.54) and in 90.8% and 9.2%, respectively, of the controls. The data suggest that in Brazilian patients with TS, the PTPN22 C1858T polymorphism may be an important genetic factor predisposing to autoimmune disease risk.