DEFECTIVE IN-VITRO COLONY FORMATION OF HEMATOPOIETIC PROGENITORS IN PATIENTS WITH CARTILAGE-HAIR HYPOPLASIA AND HISTORY OF ANEMIA

Cartilage-hair hypoplasia (CHH) is a metaphyseal chondrodysplasia with short-limbed short stature. The CHH gene has been recently mapped to chromosome 9, and a generalized defect in cellular proliferation has been suggested. Immunological and haematological abnormalities are common findings in CHH. In the present study erythroid, megakaryocyte, and granulocyte-macrophage colony formation in vitro by progenitors from bone marrow and blood was investigated in eight patients with CHH. All patients showed decreased erythroid and megakaryocyte colony formation. Only one patient had a normal granulocyte-macrophage growth, while the others showed decreased numbers of colonies. The defect in colony formation did not correlate with the haemoglobin concentration, platelet count or neutrophil count. The impaired growth was not caused by a decreased number of progenitors as shown by erythroid cultures. The erythroid progenitors were incapable of colony formation in culture conditions sufficient for colony formation by normal progenitors. In a more effectively stimulated culture assay the number of erythroid progenitors was normal or increased. Conclusion The present study shows defective in vitro colony formation in all myeloid lineages in patients with CHH, which is in accordance with the suggestion of a common cell proliferation defect in CHH.