Estudo do gene IRF6 em uma amostra de pacientes portadores de fissuras labiopalatinas não-sindrômicas por meio da triagem de mutação por sequenciamento automático

• Ano de defesa: 2007
• Autor(a) principal: Moreira, Carla Costa
• Orientador(a): Batista Junior, Eraldo Luiz
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul; Porto Alegre
• Palavras-chave em Português: ODONTOLOGIA; FISSURA LABIOPALATAL; CIRURGIA BUCOMAXILOFACIAL
• Link de acesso: http://hdl.handle.net/10923/544

Cleft lip and palate (CLP) are common orofacial anomalies. Clefts, as single entities, are classified as either non-syndromic or syndromic, whenever the characteristic clefts are associated with additional clinical signs. It has been proposed that nonsyndromic CLP alterations are related to multifactorial inheritance and in these cases the risk of a second familial case is low, around 4%. On the other hand, syndromic clefts may be caused by chromossomic aberrations, mutations or alterations of teratogenic origin. Among the syndromic forms of CLP, the Van der Woude Syndrome (VWS) is a mendelian autossomic dominant alteration. Mutations of the IRF6 gene have been linked to this alteration, which manifests the presence of pits located in the lower lip along with CLP. These are highly variable clinical entities, whose clinical overlapping signs make it difficult to properly diagnose the disease solely by its clinical features. A sound distinction between the two forms, nonsyndromic and the VWS, however, is imperative since the familial recurrence risk differs significantly between the non-syndromic (4%) and the VWS (50%). One of the molecular approaches to properly discriminate between the non-syndromic CLP and the VWS is through the analysis of the IRF6 gene. It has been estimated that twopercent of the non-syndromic CLP clinically diagnosed are indeed VWS cases. The aim of the present investigation was to assess pathological mutations of the IRF6 gene in a population originally diagnosed as non-syndromic CLP carriers in an attempt to disclose cases of the VWS syndrome.To that end, the three IRF6 exons most frequently associated with the VWS, namely exons 3, 4 and 7, were analysed through amplification and direct automated sequencing of genomic DNA isolated from 37 subjects presenting non-syndromic clefts. In this population, no pathological mutation yet characterized in the aforementoioned exons were detected. Nevertheless, two non-pathological SNPs that have been previously reported were found, the SNP rs225371 (2. 2%; 1 allele/ 44 chromossomes) and the SNP rs2235373 (6. 8% ;3 alleles/44 chromossomes). The results presented here in failed to detect VWS cases among patients diagnosed as non-syndromic L/PC as determined by sequencing of the IRF6 gene. In order to more efficiently characterize the VWS from a representative brazilian population, further studies involving more subjects, as well as individuals from other regions of the country are warranted.