Hereditary thrombocytopenia due to reduced platelet production - Report ontwo families and mutational screening of the thrombopoietin receptor gene (c-mpl)

Hereditary thrombocytopenias represent heterogeneous clinical and genetic s yndromes. They include a consistent group of families which are considered as a separate clinical entity, characterized by autosomal dominant transmis sion, incomplete penetrance in females, chronic thrombocytopenia with early age of onset and frequently increased platelet volume, without any other h ematologic abnormality. The molecular defect in these families is still unk nown. We describe 2 families in 3 generations (10 patients), and report the first study of the TPO/c-mpl system in autosomal dominant thrombocytopenia . We performed mutational screening of c-mpl coding, flanking introns and p romoter regions in 2 probands from the two families by DNA sequencing. The results do not provide evidence of c-mpl sequence alterations in either of the 2 families investigated. Moreover, the normal TPO serum levels detected in 5 patients from each family leads us to exclude the possibility of a de fect in TPO production in our families. Finally, the involvement of both c- mpl and TPO genes in the pathogenesis of thrombocytopenia in these two fami lies was excluded by negative results of linkage analysis.