RESUMO

Van der Woude Syndrome (VWS) is an autosomal craniofacial disorder characterized by lower lip pits and cleft lip and/or palate. Mutations in the interferon regulatory factor 6 (IRF6) gene have been identified in patients with VWS. To identify novel IRF6 mutations in patients affected by VWS, we screened 2 Brazilian families, sequencing the entire IRF6-coding region and flanking intronic boundaries. Two novel heterozygous mutations were identified: a frame shift mutation with deletion of G at the nucleotide position 520 in the exon 6 (520delG), and a missense single nucleotide substitution from T to A at nucleotide position 1135 in exon 8 (T1135A). By using restriction enzyme analysis, we were able to demonstrate the lack of similar mutations in unrelated healthy individuals and non-syndromic cleft lip and palate patients. Our results further confirmed that haploinsufficiency of the IRF6 gene results in VWS.

Assuntos

Indígena Americano ou Nativo do Alasca/genética , Anormalidades Craniofaciais/genética , Fatores Reguladores de Interferon/genética , Mutação/genética , Alanina/genética , Sequência de Aminoácidos , Sequência de Bases , Brasil , Análise Mutacional de DNA , Eletroforese em Gel de Ágar , Família , Humanos , Fatores Reguladores de Interferon/química , Dados de Sequência Molecular , Mapeamento por Restrição , Síndrome , Treonina/genética