title: Hereditary thrombocytopenia due to reduced platelet production--report on two families and mutational screening of the thrombopoietin receptor gene (c-mpl).
abstract: Hereditary thrombocytopenias represent heterogeneous clinical and genetic syndromes. They include a consistent group of families which are considered as a separate clinical entity, characterized by autosomal dominant transmission, incomplete penetrance in females, chronic thrombocytopenia with early age of onset and frequently increased platelet volume, without any other hematologic abnormality. The molecular defect in these families is still unknown. 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 promoter 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 defect in TPO production in our families. Finally, the involvement of both c-mpl and TPO genes in the pathogenesis of thrombocytopenia in these two families was excluded by negative results of linkage analysis.
authors.affiliation: Institute of Histology and Embriology, University of Bologna, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Tonelli
authors.forename: P
authors.initials: P
authors.lastname: Strippoli
authors.forename: A
authors.initials: A
authors.lastname: Grossi
authors.forename: A
authors.initials: A
authors.lastname: Savoia
authors.forename: A
authors.initials: A
authors.lastname: Iolascon
authors.forename: M
authors.initials: M
authors.lastname: Savino
authors.forename: M S
authors.initials: MS
authors.lastname: Teriaca
authors.forename: V
authors.initials: V
authors.lastname: Servedio
authors.forename: M
authors.initials: M
authors.lastname: Morfini
authors.forename: L
authors.initials: L
authors.lastname: Zelante
authors.forename: C
authors.initials: C
authors.lastname: Borgna-Pignatti
authors.forename: P
authors.initials: P
authors.lastname: Rosito
authors.forename: A
authors.initials: A
authors.lastname: Pession
authors.forename: G
authors.initials: G
authors.lastname: Paolucci
authors.forename: G P
authors.initials: GP
authors.lastname: Bagnara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000166:cytology*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005820:Genetic Testing; D006410:Hematopoiesis; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D013921:Thrombocytopenia / Q000209:etiology* / Q000235:genetics; D013926:Thrombopoietin / Q000097:blood / Q000235:genetics; D020506:Untranslated Regions
chemical_list: D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D020506:Untranslated Regions; C082218:MPL protein, human; D013926:Thrombopoietin