HUMAN AUTOSOMAL RECESSIVE OSTEOPETROSIS MAPS TO 11Q13, A POSITION PREDICTED BY COMPARATIVE MAPPING OF THE MURINE OSTEOSCLEROSIS (OC) MUTATION

Autosomal recessive osteopetrosis is a rare congenital disorder charac terized by the development of abnormally dense bones, acrocephaly, sev ere anemia, hepatosplenomegaly and progressive deafness and blindness, The clinical course is rapidly progressive and is lethal at a very yo ung age in the absence of a bone marrow transplant. The failure to rem odel developing bone that is the basis of the disease process is most likely due to a dysfunction of the bone resorptive cell, the osteoclas t. This phenotype is similar to that of the murine mutation osteoscler osis (oc), which is localized to proximal mouse chromosome 19. Given t he similarity between the human and murine phenotypes, we tested wheth er human osteopetrosis maps to a region of conserved synteny. Microsat ellite markers in the region of 11q12-13 were found to be linked to os teopetrosis in two consanguineous Bedouin kindreds, Recombination even ts were used to define the disease interval to an similar to 14 cM reg ion between D11S1983 and D11S2371. A maximum LOD score of 7.94 was obt ained with D11S449 at theta = 0.