An autosomal dominant thrombocytopenia gene maps to chromosomal region 10p

Abstract

The increasing number of diagnosed cases of inherited thrombocytopenias, owing to the routine practice of including platelet counts in blood tests, suggests that this condition is not so rare as expected. In the majority of cases, 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 affected by autosomal dominant thrombocytopenia. Patients showed a moderate thrombocytopenia with minimal symptoms characterized by normocellular bone marrow, normal medium platelet volume, and positive aggregation tests. Microsatellite analysis demonstrated that the disease locus (THC2) is linked to chromosome 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 was obtained with the microsatellite D10S588. These data localized the first locus of an autosomal dominant thrombocytopenia, and the subsequent identification of the gene will provide new insight into the basic mechanism of megakaryocytopoiesis disorders.

Figure 1

Family pedigree with haplotype reconstruction for informative markers on 10p11.2-12. The at-risk haplotype is boxed.

Figure 2

Schematic representation of a partial linkage map of 12 microsatellite markers located on 10p11.2-12. The mapping order and genetic distances (in cM) were obtained from the Whitehead Institute/MIT Genome Sequencing Project. The boldface segment denotes the linked interval determined by haplotype analysis.