Made available in DSpace on 2014-06-11T19:25:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-11-17Bitstream added on 2014-06-13T18:53:44Z : No. of bitstreams: 1 cruz_jb_me_botfm.pdf: 449482 bytes, checksum: 5627323423c217568fc73820cbf66a6a (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A hipófise anterior compõe-se de cinco tipos celulares que são definidos pelos hormônios que secretam. A diferenciação desses tipos celulares resulta de uma cascata temporalmente regulada de fatores transcricionais expressos no tecido hipofisário. Mutações de um desses fatores podem resultar tanto em defeitos estruturais da glândula como em deficiências hormonais, que podem ser isoladas (Déficit de hormônio do crescimento - DGH) ou combinadas (DHHC), dependendo do papel do fator transcricional mutado. A Displasia Septo – óptica (DSO) caracteriza-se pela presença de hipoplasia hipofisária, hipoplasia de nervo óptico e/ou má formações de estruturas da linha média. Foram avaliados 11 pacientes com quadro clinico de SOD, DGH e DHHC e realizado o sequenciamento genético do gene HESX1 desses indivíduos. Nos casos de DHHC foi feita uma análise adicional do gene PROP1. A mutação missense em estado de heterozigose A1772G levando a substituição N125S foi identificada em um paciente portador de DSO, no gene HESX1. Essa troca já foi previamente relatada como um polimorfismo na população Afro-Caribenha. Encontramos três pacientes portadores da variante alélica A9A e N20S no exon 1 do gene PROP1, já descritos previamente na literatura como polimorfismos. / The anterior pituitary is made of five types of cell defined according to the hormones they secrete. Differentiation among such cell types derives from a cascade of temporally regulated transcriptional factors expressed in the pituitary tissue. Mutation in one of these factors may result in both structural gland defects and hormonal deficiencies, which may be either isolated (DGH – Growth Hormone Deficiency) or combined, depending on the role of the mutated transcriptional factor. Septo-optic dysplasia (SOD) is characterized by pituitary hypoplasia, optic nerve hypoplasia and/or malformation of medium line structures. Eleven patients with a clinical state of SOD, DGH and CPHD were assessed, and genetically sequenced for the HESX1 gene. For CPHD cases, an additional analysis for the PROP1 gene was also conducted. One SOD patient was found to have a missense mutation in A1772G heterozygosis state, leading to the N125S replacement, in HESX1 gene. Such replacement has already been reported as a polymorphism in the Afro-Caribbean population. We found three patients with the alelic variation A9S and N20A in exon 1 of PROP1 gene, previously described as polymorphisms.

Resumo: A hipófise anterior compõe-se de cinco tipos celulares que são definidos pelos hormônios que secretam. A diferenciação desses tipos celulares resulta de uma cascata temporalmente regulada de fatores transcricionais expressos no tecido hipofisário. Mutações de um desses fatores podem resultar tanto em defeitos estruturais da glândula como em deficiências hormonais, que podem ser isoladas (Déficit de hormônio do crescimento - DGH) ou combinadas (DHHC), dependendo do papel do fator transcricional mutado. A Displasia Septo - óptica (DSO) caracteriza-se pela presença de hipoplasia hipofisária, hipoplasia de nervo óptico e/ou má formações de estruturas da linha média. Foram avaliados 11 pacientes com quadro clinico de SOD, DGH e DHHC e realizado o sequenciamento genético do gene HESX1 desses indivíduos. Nos casos de DHHC foi feita uma análise adicional do gene PROP1. A mutação missense em estado de heterozigose A1772G levando a substituição N125S foi identificada em um paciente portador de DSO, no gene HESX1. Essa troca já foi previamente relatada como um polimorfismo na população Afro-Caribenha. Encontramos três pacientes portadores da variante alélica A9A e N20S no exon 1 do gene PROP1, já descritos previamente na literatura como polimorfismos. / Abstract: The anterior pituitary is made of five types of cell defined according to the hormones they secrete. Differentiation among such cell types derives from a cascade of temporally regulated transcriptional factors expressed in the pituitary tissue. Mutation in one of these factors may result in both structural gland defects and hormonal deficiencies, which may be either isolated (DGH - Growth Hormone Deficiency) or combined, depending on the role of the mutated transcriptional factor. Septo-optic dysplasia (SOD) is characterized by pituitary hypoplasia, optic nerve hypoplasia and/or malformation of medium line structures. Eleven patients with a clinical state of SOD, DGH and CPHD were assessed, and genetically sequenced for the HESX1 gene. For CPHD cases, an additional analysis for the PROP1 gene was also conducted. One SOD patient was found to have a missense mutation in A1772G heterozygosis state, leading to the N125S replacement, in HESX1 gene. Such replacement has already been reported as a polymorphism in the Afro-Caribbean population. We found three patients with the alelic variation A9S and N20A in exon 1 of PROP1 gene, previously described as polymorphisms. / Orientador: Célia Regina Nogueira / Coorientador: Denise Perone / Mestre

Genetic and Hormonal Regulation of Children's Growth MUDr. Jan Vosáhlo Abstract Growth in childhood is a complex process of changing the body, which can be disrupted by various illnesses including endocrine disorders, particularly growth hormone deficiency. Tumors or other processes affecting hypothalamic-pituitary area can be a postnatal cause of GHD; prenatal causes include 1) developmental disorders of the pituitary as part of complex syndromes, 2) developmental disorders of the pituitary due to defects in regulatory genes and 3) defects in genes involved in the synthesis and secretion of GH. The first topic of the thesis was septo-optic dysplasia - a complex syndrome involving optic nerve hypoplasia, structural brain abnormalities and pituitary dysfunctions. We extensively described phenotype in 11 Czech patients; we observed both complete SOD and incomplete forms variously combining two of the three main components of the syndrome. The cohort then became a part of an international study of 68 patients, in which we studied the phenotype in dependence on the brain morphology. We found correlation between the severity of clinical symptoms and the degree of septum pellucidum abnormities and also a correlation between hippocampus and falx abnormities and neurological symptoms. As the second topic we studied...

Genetic and Hormonal Regulation of Children's Growth MUDr. Jan Vosáhlo Abstract Growth in childhood is a complex process of changing the body, which can be disrupted by various illnesses including endocrine disorders, particularly growth hormone deficiency. Tumors or other processes affecting hypothalamic-pituitary area can be a postnatal cause of GHD; prenatal causes include 1) developmental disorders of the pituitary as part of complex syndromes, 2) developmental disorders of the pituitary due to defects in regulatory genes and 3) defects in genes involved in the synthesis and secretion of GH. The first topic of the thesis was septo-optic dysplasia - a complex syndrome involving optic nerve hypoplasia, structural brain abnormalities and pituitary dysfunctions. We extensively described phenotype in 11 Czech patients; we observed both complete SOD and incomplete forms variously combining two of the three main components of the syndrome. The cohort then became a part of an international study of 68 patients, in which we studied the phenotype in dependence on the brain morphology. We found correlation between the severity of clinical symptoms and the degree of septum pellucidum abnormities and also a correlation between hippocampus and falx abnormities and neurological symptoms. As the second topic we studied...

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