FREQUENCY OF GERMLINE MUTATIONS IN PHEOCHROMOCYTOMA ASSOCIATED FAMILIAL SYNDROMES IN AN ARGENTINE POPULATION

DRA GABRIELA SANSO; ANA VIEITES; GLORIA LEVIN; BARONTINI MARTA

Lima

Congreso; -XX REUNION DE LA SOCIEDAD LATINOAMERICANA DE ENDOCRINOLOGIA PEDIATRICA; 2008

More than 25% of pheochromocytoma are hereditary. The inherited pheo-associated syndromes are MEN 2 on account of mutations of the ret gene, VHL on account of mutation of the vhl gene and pheochromocytoma-paraganglioma (Pheo-pgl) syndromes caused by mutations of of the SDHB, SDHD and SDHC genes. The aim of this work was to evaluate the frequency of germ-line mutations in the genes coding for the vhl, ret and SDH (B y D) in a sample of 72 Argentine index patients (4-71 y) having the clinical features of pheo associated familial syndromes. The diagnosis was supported by clinical, biochemical (VMA, E, NE and Calcitonin) imaging (I131 MIBG, TAC, RMN, PET) and confirmed at surgery. We have identified 34 MEN 2A 47%, 5 CMTF 6.9%, 12 MEN 2B 16.6%, 12 VHL 16.6%, 2 SDHD 2.7% and 7 SDHB 9.7%. We have been able to find 12 sequence variants in MEN 2, 3 in SDHB, 2 in SDHD and 10 in VHL. The prevalence of the VHL was high in the young population (under 21y, 10/12), in contrast with the adult population that showed the greatest prevalence of MEN 2 (38/50). Remarkably the sequence variants g300-304delCCTCA was present in high frequency in a group of SDHB patients with malignant pheos being this the only correlations genotype-phenotype that we found. This study show the mutations found in an argrntine population and contributes four novel germ-line vhl mutations and two novel germ-line SDHB mutations.