A prevalência do polimorfismo A1298C e não do C677T do gene MTHFR está relacionada à ocorrência de aneuploidias cromossômicas em mulheres brasileiras portadoras da síndrome de Turner

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.INTRODUÇÃO: Disfunções no metabolismo dos folatos podem resultar em hipometilação do DNA e na segregação cromossômica anormal. Dois polimorfismos comuns no gene MTHFR (C677T e A1298C) reduzem a atividade da enzima e, quando associados a estudos de aneuploidias apresentam resultados conflitantes. O objetivo do presente estudo foi a análise dos polimorfismos do gene MTHFR em mulheres portadoras da síndrome de Turner e em indivíduos de grupo-controle, correlacionando os achados ao mecanismo de formação de aneuploidias cromossômicas. MÉTODOS: Foram estudadas 140 portadoras da síndrome de Turner sendo 36 com mosaicismo cromossômico e 104 não-mosaicos, e um grupo-controle composto por 209 mulheres férteis e saudáveis sem história de prole com aneuplodia. Os polimorfismos MTHFR C677T e A1298C foram estudados por RFLP-PCR e os resultados analisados estatisticamente. RESULTADOS: A freqüência dos genótipos MTHFR 677CC, 677CT e 677TT nas pacientes portadoras de síndrome de Turner e mosaicismo cromossômico foi, respectivamente, 58,3%, 38,9% e 2,8%. Das pacientes portadoras de síndrome de Turner não-mosaico, 47,1% apresentaram o genótipo 677CC, 45,2% o genótipo 677CT e 7,7% apresentaram o genótipo 677TT. Nos 209 indivíduos do grupo-controle, os genótipos 677CC, 677CT e 677TT foram encontrados nas seguintes freqüências: 48,3%, 42,1% e 9,6%, respectivamente. Quanto ao polimorfismo A1298C, as portadoras de síndrome de Turner e mosaicismo cromossômico apresentaram os genótipos 1298AA, 1298AC e 1298CC nas seguintes freqüências: 58,3%, 27,8% e 13,9%, respectivamente. Já nas portadoras de Síndrome de Turner não-mosaico, o genótipo 1298AA foi encontrado em 36,5%, o genótipo 1298AC em 39,4% e o genótipo 1298 CC em 22,1% . No grupo-controle, os genótipos 1298AA, 1298AC e 1298CC estavam presentes nas freqüências 52,6%, 40,7% e 6,7%. CONCLUSÃO: Não foi observada correlação entre o polimorfismo C677T do gene MTHFR e a aneuploidia cromossômica presente nas portadoras de síndrome de Turner. O polimorfismo A1298C do gene MTHFR, principalmente o genótipo 1298CC, foi mais freqüente nas portadoras de síndrome de Turner, sugerindo seu envolvimento no mecanismo de formação de aneuploidias cromossômicas.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Federal University of São Paulo Department of Medicine Endocrinology DivisionFederal University of São Paulo Department of Morphology and Genetics Genetics DivisionUniversity of Cuiabá General Hospital Medical Genetics and Molecular Biology UnitGenetics Division of Medicine College from ABCUNIFESP, Department of Medicine Endocrinology DivisionUNIFESP, Department of Morphology and Genetics Genetics DivisionSciEL

Study clinical-epidemic of patients with the Turner Syndrome users' to SUS in the state of Mato Grosso

In the feminine population with short stature with the Turner Syndrome it is a differential obligatory diagnosis this study aims at knowing its clinical epidemic characteristics to help in the planning of the actions of health care in this population. The prevalence in the State of Mato Grosso is unknown and the 17 cases reported were more than expected for a well-known frequency of 1:2000 to 1:5000. A descriptive study of series of patients' cases was accomplished with the Turner Syndrome in using the Growth Hormone with cariotip confirmation filled in the SUS until July 2004. Most of them were from Cuiabá and Várzea Grande, 64,71% were born to term, 23,52% were low weight at birth, 70,59% (n=12/17) presented short stature at the diagnosis and had normal weight (92,31%); 94,12% (n=16/17) was diagnosed over age 6 and the beginning of the treatment was late (7,08 and 15,50 years of age). The family was responsible for 82.35% of the diagnosis suspicion and the confirmation was made mainly by the Pediatrician and the Endocrinologist. In 82.35% of the patients dysmorphical terations reported as the most frequent was the short stature (82.35%) which was the main reason for looking for a doctor. The most frequent type of karyotype presentation was 45X (n=7/17, 41.18%), but most of them mosaicism (n=10/17, 58.82%), with low frequency of solicitation of markers of chromosome Y, 35.29% (n=6/17). The main reactions of the family when they knew about the disease weres adness, a feeling of impotence and concern about the stature. When asked about the use of the Growth Hormone, they reported that it was due to short stature or the Turner Syndrome. 58.82 % reported mild to great difficulties in the access to SUS to get medicine for the treatment due to bureaucratic problems. The annual expenses with the Growth Hormone, in these patients correspond approximately to 16% of the total expense of the State

Prevalence of Hyposalivation in Patients with Systemic Lupus Erythematosus in a Brazilian Subpopulation

Background. Systemic lupus erythematosus (SLE) is a chronic inflammatory, multisystem, and autoimmune disease. Objective. The aim of this study was to describe the prevalence of hyposalivation in SLE patients and evaluate factors associated. Methods. This is a cross-sectional study developed at the Cuiaba University General Hospital (UNIC-HGU), Mato Grosso, Brazil. The study population consisted of female SLE patients treated at this hospital from 06/2010 to 12/2012. Unstimulated salivary flow rates (SFRs) were measured. Descriptive and inferential analyses were performed in all cases using a significance level P<0.05. Results. The results showed that 79% of patients with systemic lupus erythematosus suffered from hyposalivation and that the disease activity and age in years were the factors that resulted in statistically significant differences. Conclusion. The activity of the disease, age >27 years, and the drugs used were factors associated with hyposalivation, resulting in a statistically significant decrease in saliva production

Mutations, Clinical Findings and Survival Estimates in South American Patients with X-Linked Adrenoleukodystrophy

In this study, we analyzed the ABCD1 gene in X-linked adrenoleukodystrophy (X-ALD) patients and relatives from 38 unrelated families from South America, as well as phenotypic proportions, survival estimates, and the potential effect of geographical origin in clinical characteristics

Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly

Functional polymorphisms in the p53 pathway genes on the genetic susceptibility to zika virus teratogenesis

Congenital Zika Syndrome (CZS) occurs in up to 42% of individuals exposed to ZIKV prenatally. Deregulation in gene expression and protein levels of components of the p53 signaling pathway, such as p53 and MDM2, due to ZIKV infection has been reported. Here, we evaluate functional polymorphisms in genes of the p53 signaling pathway as risk factors to CZS. Forty children born with CZS and forty-eight children exposed to ZIKV, but born without congenital anomalies were included in this study. Gestational and sociodemographic information as well as the genotypic and allelic frequencies of functional polymorphisms in TP53, MDM2, MIR605 and LIF genes were compared between the two groups. We found children with CZS exposed predominantly in the first trimester and controls in the third trimester (p<0.001). Moreover, children with CZS were predominantly from families with a lower socioeconomic level (p=0.008). We did not find a statistically significant association between the investigated polymorphisms and development of CZS; however, by comparing individuals with CZS and lissencephaly or without lissencephaly, we found a significative difference in the allelic frequencies of the TP53 rs1042522, which is associated with a more potent p53-induced apoptosis (p=0.007). Our findings suggest that the TP53 rs1042522 polymorphism should be better investigate as a genetic risk factor for the development of lissencephaly in children with CZS

Genetical, clinical, and molecular cytogenetical study of patients with isolated lissencephaly sequence

A lisencefalia classica (LC) e uma malformacao cerebral caracterizada por uma superficie cerebral lisa devido a um disturbio na migracao neuronal. A LC tem sido observada em associacao com a Sindrome de Miller-Dieker (SMD) e a Sequencia da Lisencefalia Isolada (SLI). A literatura mostra que delecoes visiveis ou submicroscopicas ocorrem no mesmo loco entre 10 a 40 por cento dos pacientes com SLI. Um gene conhecido como LIS1 foi mapeado em l7pl3.3 e suas alteracoes tem sido responsaveis pela maioria dos casos de LC. Um outro gene foi identificado em Xq22-q23 (XLIS) e esta relacionado a LC ligada ao X e aos quadros de Heterotopia com Banda Sucortical. O presente estudo aborda os aspectos clinicos, radiologicos e citogeneticos em 10 pacientes com SLI. A avaliacao clinica e radiologica, os pacientes foram categorizados como portadores da SLI. A abordagem citogenetica foi realizada pelas tecnicas de citogenetica classica e pela metolodogia da hibridacao in situ com fluorescencia (FISH) com a sonda do marcador Dl7S379 (Oncor©). Todos pacientes mostravam um cariotipo normal e uma paciente (caso 2) revelou uma microdelecao pelo metodo da FISH. A delecao era de novo e foi procedido uma amplificacao de um fragmento de Dl7S379, atraves da PCR, com o objetivo de identificar a origem parental da delecao. Para tanto, foram utilizadas sequencia iniciadoras que flanqueiam uma regiao que contem um polimorfismo de repeticao CA. Contudo, a familia estudada nao foi informativa ara esta abordagemBV UNIFESP: Teses e dissertaçõe

Estudo genético-clinico, radiológico e anatomopatologico de osteocondrodisplasias letais

BV UNIFESP: Teses e dissertaçõe