MOLECULAR DIAGNOSIS IN AN ARGENTINE FAMILY WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 (MEN-1)

MEN-1 is a hereditary autosomal dominant syndrome characterized by the involvement of parathyroid glands, pancreatic islet cells and anterio r pituitary gland. Today molecular genetics permit gene carrier analys is to compare the data obtained with the clinical biochemical tests. T he twenty living members of the first, second and third generation of a family with MEN-1 were studied to determine the presence of genetic markers in MEN-1 loci 11q13, by linkage analysis and in affected indiv iduals by biochemical tests and clinical examination. Two very informa tive polymorphic markers immediately Ranking the MEN-1 gene on chromos ome 11 band q13 were detected: PYGM and D11S987, haplotypes segregated by two members of the second generation, inherited from their father and two of the third generation: the affected one and one presymptomat ic. The third generation had the affected member with renal stones and elevated PTH, PRL and glucagon. The presymptomatic carrier of MEN-1 a llele showed elevated PTH. Among the members who inherited the normal allele we found one with elevated gastrin, one with elevated glucagon and one with elevated PTH, all asymptomatic. Of one Argentine family s tudied, molecular diagnosis allowed us to detect one presymptomatic ca rrier in the members at risk. As suggested by the available literature , accuracy of molecular diagnosis seems to make it the test of choice to exclude those members at-risk for MEN-1 inheriting the normal allel e.