ABSTRACT
A Síndrome Blefaroqueilodôntica (BCD) e os Defeitos de Linha Média Facial com Hipertelorismo (DLMFH) são defeitos craniofaciais raros. Por esse motivo, os estudos de grandes casuísticas têm sido limitados. Contribuição científica significativa neste assunto tem sido dada por nosso grupo, que delineou características clínicas e diretrizes para seguimento de longo prazo e evidenciou achados neuroradiológicos em ambas as anomalias. Embasado nesses achados preliminares e evidências recentes da literatura pertinente, foi possível estabelecer uma estratégia inicial para investigação etiológica da BCD e dos DLMFH, sendo os objetivos desse projeto: investigar a etiologia da BCD nos indivíduos afetados pela síndrome, por meio de estudo dos genes candidatos IRF6, P63, OSR2, TBX10, FOXE1, SHH, FGF8 e PAX3; pesquisar, nos indivíduos com DLMFH, a presença de mutações nos genes candidatos SHH, FGF8 e PAX3; identificar, em ambas as malformações, possíveis alterações cromossômicas; e, por último, associar os achados clínicos detectados nas investigações anteriores aos possíveis achados moleculares. Foram utilizadas técnicas de sequenciamento direto, array-CGH, genotipagem automática e hibridação in situ por fluorescência. Não foi possível relacionar nenhuma mutação pontual nos genes estudados associadas às malformações em questão, pois não foram encontradas alterações gênicas patogênicas. Entretanto foram detectadas em pacientes com DLFMH três aberrações cromossômicas em regiões distintas do genoma, tratando-se de um caso de duplicação no cromossomo...
The Blepharocheilodontic Syndrome (BCD) and Midline Facial Defects with Ocular Hypertelorism (MFDH) are rare craniofacial anomalies. Considering the rarity of these two groups of congenital defects, studies with large casuistry have been limited. Our group has significantly contributed to the scientific knowledge about both anomalies, delineating clinical characteristics, evidencing neurological findings and designing protocols for long term follow-up. Based in these preliminary findings and recent evidences of pertinent literature, it was possible to determine an initial etiologic investigation strategy for the BCD and the MFDH. The objectives of this project are to investigate the etiology of the BCD in affected individuals through IRF6, P63, OSR2, TBX10, FOXE1, SHH, FGF8 and PAX3 candidate genes study; to search MFDH patients for mutations in the SHH, FGF8 and PAX3 candidate genes; to identify, in both syndromes...
Subject(s)
Humans , Male , Female , Blepharophimosis/genetics , Chromosome Aberrations , Craniofacial Abnormalities , Hypertelorism , Cleft Lip , Cytogenetic Analysis , Skull/embryology , GenesABSTRACT
OBJECTIVE: To describe the first report on a three-generation family presenting typical features of Saethre-Chotzen syndrome, in which the Q289P mutation in the FGFR2 gene was detected. DESIGN: Dysmorphological evaluation was performed by a clinical geneticist. Direct sequencing of the polymerase chain reaction-amplified coding region of TWIST and screening for the P250R mutation in the FGFR3 gene were performed. Exons IIIa and IIIc of FGFR2 were sequenced also. The mutation was confirmed by both restriction-enzyme digestion and allelic-specific polymerase chain reaction. RESULTS: Neither TWIST gene analysis nor analysis of the P250R mutation on gene FGFR3 showed mutation within the coding sequence. A nucleotide change from CAG to CCG in exon IIIa of the FGFR2 gene that caused a Q289P mutation was detected, although exon IIIc in the propositus was normal. These same results were detected in his mother, but no other members of the kindred presented clinical features consistent with Saethre-Chotzen syndrome. CONCLUSIONS: This mutation was previously reported in individuals with Crouzon and Jackson-Weiss syndromes. The FGFR2 mutation in the family with Saethre-Chotzen syndrome herein reported reinforces the idea of an interaction among TWIST and FGFR genes during development. Absence of the Q289P mutation in some affected individuals in this family is discussed.