Estudo de craniossinostoses por meio de investigação de regiões genomicas especificas

AUTOR(ES)
DATA DE PUBLICAÇÃO

2005

RESUMO

Craniosynostosis refers to the premature fusion of one or more of the cranial sutures, affecting about 0,4-1/1000 newborns. More than 100 distinct genetic syndromes with craniosynostosis have been described. Most of them exhibit autosomal dominant transmission and variable expressivity. Clinical diagnostic is also ofien difficulted by the overlapping features among different conditions. Maintenance of suture patency depends on regulating a complex array of factors, including FGFR1, FGFR2, FGFR3, MSX2 and TWIST. Mutations in these genes are know to cause craniosynostosis, the former by constitutive activation and the latter by haploinsufficiency. In order to identify mutations in the main regions of these genes in individuais with syndromic or isolated craniosynostosis, 13 families and 8 isolated cases were screened. The investigation protocol included dysmorphological evaluation and high resolution citogenetics analysis. Molecular investigation was based upon an algorrithm previously described and literature review. It included the P252R mutation of FGFR1, mutations in exon 8 and 10 of FGFR2 gene, P250R of FGFR3 gene, and mutations in exon 1 of TWIST gene. The mutation L154P in MSX2 were investigated in individuais with parietal foramina. One individual with SCS showed an chromosomal aberration involving the region of TWIST gene (46, XX add 7(p21». In FGFR2, mutations in exon 8 were detected in 4/21, including a previously undescribed one on SSC (FGFR2 Q289P); mutations in exon 10 were detected in 2/21. One family with SCS had a P250R FGFR3 mutation and 3 alterations in exon 1 of the TWIST gene. Investigations in FGFR1 were normal, as well as the MSX2 gene in individuais with parietal foramina. Among MCA individuais, no molecular abnormalities were found in the studied regions. This study reinforces the molecular heterogeneity of craniosynostosis and suggests the screening of FGFR2 gene as complementar step in SCS investigation. In the future, studies could elucidate the etiology of parietal foramina and MCA individuais herein evaluated

ASSUNTO(S)

fator de crescimento fibroblastico - receptores cranio - anomalias e deformidades craniossinostose

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