Aims: We aimed to investigate whether two genes recently reported to cause predisposition to familial pituitary adenomas, AlP and P27/Kip1, playa role in the pituitary phenotype of the MEN1 Brazilian family.
Methods: Twenty-eight MEN1 patients were fully examined and separated into three groups according to their pituitary phenotype: cases that developed PIT at early ages (group A), cases with invasive PIT (group B), and cases without PIT (group C). The entire coding region and intron/exon frontiers of the AlP and P27/Kip1 genes were directly sequenced.
Results: No mutation was found in either AlP or P27/ Kip1 genes. One single nucleotide change C> T (rs641 081, Q228K) was found in the AlP gene. Two nucleotide changes, a C> T change in the 5'UTR promoter region (rs59917413) and a G> T change (rs2066827, V1 09L) in exon 1 of the P27/ Kip1 gene, were identified. The rs641 081 and rs59917413 variants were found in all three groups. The rs2066827 variant segregated with both groups A and C, whereas it was not present in group B.
Conclusions: We concluded that high frequency, aggressiveness, and time-onset of pituitary disease in this large MEN1 family with a possible pituitary variant could not be attributed to sequence variants of the recently identified pituitary genes AlP and P27/Kip1.
References:
1. Olufemi SE,etal. Common ancestral mutation in the MEN1 gene is likely responsible for the prolactinoma variant of MEN 1 (MEN1 Burin) in four kindreds from Newfoundland. Human Mutation 1998 11 264-269.
2. Louren~o-Jr O.M. et al. Multiple endocrine neoplasia type 1 in Brazil: MEN 1 founding mutation, clinical features and bone minerai density profile. submitted, 2008.
Support: RAT. is recipient of Coordenac;ao de Aperfeic;oamento de Pessoal de Nfvel Superior (CAPES) PhD fellowship. D.M.L is recipient of Fundac;ao Faculdade de Medicina (FFM) pos-doctoral fellowship.