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. Candidate gene analysis is in progress for proximal symphalangism. In the analysis of Type II collagen disorders, a rapid method of detecting nonsense mutations in families with Stickler syndrome has been developed. Over the past year, the Skeletal Genome Anatomy Project (SGAP) has been initiated to find novel genes expressed in skeletal tissue. EST sequencing was begun on two 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 3700 ESTs have been sequenced to date, resulting in the identification of approximately 50 novel sequences.
