Estudos moleculares de craniossinostoses com enfase na mutação Q289P do gene FGFR2 / Molecular of craniosynostosis and the mutation Q289P in the FGFR2 gene

AUTOR(ES)

Bernardo Lamartine Nogueira Passarinho

DATA DE PUBLICAÇÃO

2008

RESUMO

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.

ASSUNTO(S)

craniosynostoses craniossinostose

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