HUM-MOLGEN DIAGnostics/Clinical Research


22 November 1996
Hereditary bone dysplasia (McKusick #112250)

Dear Colleague:

We are studying the natural history and molecular biology of a rare bone dysplasia and are seeking additional patients and their families. 3Hereditary bone dysplasia with malignant changes2, is an autosomal dominant (McKusick9s Mendelian Inheritance in Man #112250), bone disorder characterized by diaphyseal medullary stenosis, necrosis, and infarctions with overlying cortical thickening of the long bones. The disease typically manifests itself in the form of pathologic fractures secondary to minimal trauma with subsequent poor healing or non-union of the fracture and a predisposition to the formation of a highly malignant fibrous histiocytoma / fibrosarcoma in an infarcted lesion in the second to fifth decades of life (Ann Int Med 78:902; and, J Bone & Joint Surgery. 68A:1079, 1986). We have recently identified the fourth known family with this rare dysplasia and described a more tumor-sensitive screening agent (Ped Radiol 26:675, 1996). The Department of Human Genetics at the Mount Sinai School of Medicine offers expertise in the application of molecular, biochemical, cytogenetic, and somatic cell approaches for the study of genetic diseases and outstanding clinical services dedicated to the care of affected individuals and their families. Our laboratory has most recently mapped and identified the pycnodysostosis gene (Nat Genet 10:235, 1995; Science 273:1236, 1996, respectively) and has also refined the critical region for cleidocranial dysplasia (Am J Med Genet. 58:200, 1995). In collaboration with the original investigators, who provided the earliest clinical descriptions of 3hereditary bone dysplasia2, we have initiated a positional cloning project to identify the causative disease gene. Additionally, we are defining the natural history and phenotypic variability of this disorder. We are actively searching for additional patients and their families to facilitate these studies. If you are aware of any patients who might be willing to participate, kindly contact us by telephone (212)241-6947, fax (212)360-1809 or e-mail ( All research will be performed under IRB approval and all samples will be effectively protected against identification of the patient/donor. Thank you in advance for your kind cooperation in this matter. Sincerely yours,

John A. Martignetti M.D., Ph.D.
Departments of Human Genetics and Pediatrics
Mount Sinai School of Medicine
Department of Human Genetics
New York, N.Y. 10029