An autosomal dominant thrombocytopenia gene maps to chromosomal region 10p

The increasing number of diagnosed cases of inherited thrombocytopenias, ow ing to the routine practice of including platelet counts in blood tests, su ggests that this condition is not so rare as expected. In the majority of c ases, the molecular basis of the disease is unknown, although the defect is likely to affect thrombocytopoiesis and regulation of the normal platelet count. Here we report a genomewide search in a large Italian family affecte d by autosomal dominant thrombocytopenia. Patients showed a moderate thromb ocytopenia with minimal symptoms characterized by normocellular bone marrow , normal medium platelet volume, and positive aggregation tests. Microsatel lite analysis demonstrated that the disease locus (THC2) is linked to chrom osome 10p11.1-12, within a candidate region of 6 cM between markers D10S586 and D19S1639. A maximum LOD score of 8.12 at recombination fraction .00 wa s obtained with the microsatellite D10S588. These data localized the first locus of an autosomal dominant thrombocytopenia, and the subsequent identif ication of the gene will provide new insight into the basic mechanism of me gakaryocytopoiesis disorders.