This study is to identify disease genes causing a variety of human skeletal dysplasias, and to identify relationships between the identified mutations and the resulting phenotypes. Disorders studied include pycnodysostosis, Ellis-van Crevald (EvC) syndrome, Cartilage- hair hypoplasia, proximal symphalangism, Brachydactyly type C and the type II collagen disorders. Positional cloning studies are continuing in the effort to find the Ellis-van Crevald, Cartilage-hair hypoplasia and Brachydactyly type C genes. In the past year, the gene for proximal symphalangism has been identified as the Noggin gene on chromosome 17. Significant progress has been made toward the identification of the EVC gene, and several candidates have been excluded in the search for CHH. The Skeletal Genome Anatomy Project (SGAP) continues to find novel genes expressed in skeletal tissue. EST sequencing on two cDNA libraries constructed by Dr. Pam Robey and her colleagues at the National Institute of Dental Research. These include bone marrow stromal cell cDNA library and a cDNA library from normal human trabecular bone. A total of 6000 ESTs have been sequenced to date, resulting in the identification of more than 60 novel sequences. The laboratory is developing methods to assess the expression of cDNAs found in these and other skeletal libraries. - skeletal dysplasia, natural history, connective tissue disorder, SGAP, bone, cartilage, gene identification - Human Subjects
