Title page, table of contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / This thesis describes the structure of normal cranial sutures and those which have undergone premature fusion or craniosyntosis. It also reports the results of investigations of human sutures to identify possible underlying aetiologies which result in premature fusion. The study also investigates the effects of these abnormally fused sutures on the affected individuals, in particular the secondary effect on intercranial volume both in those with just a single affected suture and those with multiple sutures involved as part of a syndrome. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1277057 / Thesis (Ph.D.) -- University of Adelaide, School of Dentistry, 2007

Title page, table of contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / This thesis describes the structure of normal cranial sutures and those which have undergone premature fusion or craniosyntosis. It also reports the results of investigations of human sutures to identify possible underlying aetiologies which result in premature fusion. The study also investigates the effects of these abnormally fused sutures on the affected individuals, in particular the secondary effect on intercranial volume both in those with just a single affected suture and those with multiple sutures involved as part of a syndrome. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1277057 / Thesis (Ph.D.) -- University of Adelaide, School of Dentistry, 2007

Thesis (Ph.D.)-- University of Adelaide, Dept. of Paediatrics, 1998. / Copies of author's previously published works inserted. Bibliography: leaves 195-222.

Orientador: Vera Lucia Gil da Silva Lopes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-10T14:39:46Z (GMT). No. of bitstreams: 1 Passarinho_BernardoLamartineNogueira_M.pdf: 1529378 bytes, checksum: 50b6bc3b336a69747186f002deac57e3 (MD5) Previous issue date: 2008 / Resumo: A família dos genes FGFRs está envolvida na via molecular que participa na modulação do desenvolvimento craniofacial e de membros em humanos. Mutações nos genes FGFR1, FGFR2 e FGFR3 têm sido associadas a uma variedade de fenótipos diferentes com presença de craniossinostose ou outras deformidades ósseas. O gene FGFR2 codifica um receptor do fator de crescimento de fibroblastos. No éxon IIIa deste gene, foi identificada a mutação Q289P, a qual foi descrita em casos isolados e em famílias com craniossinostoses sindrômicas, incluindo uma com S. de Jackson-Weiss, outra com S. de Pfeiffer e uma, relatada por nosso grupo de pesquisa, com quadro clínico de S. de Saethre-Chotzen. Nesta última, entretanto, como nem todos os indivíduos afetados apresentavam esta mutação, algumas hipóteses foram aventadas. Entre elas, a de que esta mutação produza uma proteína moduladora do mecanismo do fechamento prematuro das suturas, ou, ainda que esta seja, na verdade, um polimorfismo de baixa freqüência não relacionado a craniossinostoses. O presente trabalho teve como objetivo testar estas hipóteses. Foi realizada a análise populacional da referida mutação em dois grupos constituídos por 40 indivíduos portadores de síndromes de craniossinostoses e 200 indivíduos de uma amostra da população. Foram pesquisadas mutações nos principais pontos relacionados à craniossinostoses nos genes FGFR1, FGFR2 e FGFR3 nos indivíduos da família-índice que já havia sido previamente investigada para mutações no gene TWIST1. Foram também aplicados testes in silico, a fim de simular os efeitos da mutação Q289P na proteína e prever seu potencial deletério. A mutação Q289P não foi identificada nos grupos controle e de portadores de síndromes de craniossinostoses. De acordo com os achados obtidos, sugere-se que a mutação Q289P seja deletéria, rara e associada apenas ao fenótipo craniano, e não fortemente associada com o fenótipo facial e neurológico presente em alguns membros da família estudada. Existem fortes indícios de que a mutação Q289P no gene FGFR2 esteja relacionada à ocorrência de craniossinostoses. Estudos futuros de investigação experimental da função protéica poderão contribuir para melhor esclarecer os mecanismos patogênicos envolvidos na fusão precoce das suturas cranianas / Abstract: The FGFRs family is involved in the molecular pathway which plays a role in modulation of the craniofacial and members development in humans. Mutations in genes FGFR1, FGFR2 and FGFR3 have been associated to different phenotypes presenting craniosynostosis and other bone diseases. The FGFR2 gene codifies a fibroblast growth factor receptor. The mutation Q289P was identified in the IIIa exon of this gene, described in isolated cases and some craniosynostosis syndromes, including a Jackson-Weiss family, a Pfeiffer family, a Crouzon family and a Saethre-Chotzen family. The latter family was previously reported by FREITAS et al. (2006). In this specific family, all of the patients who had the Q289P mutation presented craniosynostosis, but not all of those who had facial and neurological features had the mutation, therefore some hypothesis were suggested. The mutation could generate a modified regulatory protein of skull sutures closure, or the mutation could be a low frequency polymorphism or it can be completely responsible for the Saethre-Chotzen features found in the affected members of the family. The aim of this study was to test those hypotheses. A population analysis was performed in a group of 200 control individuals and a group of 40 nonrelated syndromic craniosynostosis individuals. Secondary mutations were searched in the FGFR1, FGFR2 and FGFR3 genes in the family first described by FREITAS and in the craniosynostosis group. The TWIST1 gene was investigated in the syndromic craniosynostosis individual¿s group but, in the analyzed family, this gene has been previously tested by NASCIMENTO et al., (2004). Also, computational approaches were applied to simulate the effects of the analyzed mutation in the protein and predict its deleterious potencial. According to those findings, we suggest that the Q289P mutation is deleterious and associated to the craniosynostosis phenotype only, and not strongly related to the facial and neurological phenotype / Mestrado / Ciencias Biomedicas / Mestre em Ciências Médicas

Thesis (M.S.)--University of Michigan, 2004. / Includes bibliographical references.

Thesis (Ph.D.) in Biochemistry and Molecular Biology--University of Maine, 2007. / Includes vita. Includes bibliographical references (leaves 102-111).

No description available.

Copies of author's previously published works inserted. / Bibliography: leaves 195-222. / x, 222, [46] leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Aims to identify genes involved in craniosynostosis and to characterize mutations of these genes. / Thesis (Ph.D.)--University of Adelaide, Dept. of Paediatrics, 1998

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 94-106).

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 137-153).