RESUMO
BACKGROUND: Anorectal malformations (congenital absence of the anal opening) are among the most common pediatric surgical problems and carry a significant chronic morbidity. METHODS: Direct sequencing was used to screen 88 anorectal malformations patients for mutations and polymorphisms in SHH and GLI3. These genes were chosen according to the phenotype presented by mutant mice and their expression patterns. RESULTS: We report on 10 GLI3 variants (IVS3+141C>G, T183A, IVS4+124T>C, IVS7+17G>A, IVS8+1 G>C, N503N, P941P, P998L, A1005A, A1039A) and four SHH mutation/variants (IVS1-49C>T, IVS2+111A>C, L214L, G290D). CONCLUSIONS: These variants are not over-represented in the healthy population and most are predicted to be benign. This study conveys the problematic assessment of the pathogenic role in disease of rare point mutations and variants.
