Oculodentodigital dysplasia (ODDD) is a syndrome with an autosomal dominant pattern of inheritance. The phenotype includes dental, craniofacial, ocular, hand, foot, and long bone abnormalities. Central nervous system signs and symptoms related to white matter degeneration can occur in some ODDD patients. These neurological manifestations and some dysmorphic features may be more severe or occur at an earlier age in successive generations of ODDD kindreds, suggestive of a phenomenon known as """"""""genetic anticipation."""""""" The Principal Investigator has confirmed linkage of this condition to chromosome 6 and narrowed the candidate region to a 1.01 to 2.87 cM region between DNA markers D6S266 and D6S1639. This candidate region physically maps within two overlapping YAC clones. The overall goal of this project is to identify the gene associated with ODDD.
The specific aims of the proposal are to 1.) Ascertain additional ODDD families and sporadic cases, refine the ODDD genetic map location by linkage and haplotype analyses, and refine the ODDD physical map location by constructing YAC, PAC, BAC, and cosmid contigs; 2.) Isolate candidate cDNAs in the critical region; 3.) Identify the disease gene by detecting mutations; and 4.) Perform phenotype/genotype correlations. Isolations of the gene will be important for accurate diagnosis and identification of genetic factors involved in dental, craniofacial, ocular, limb, bone, and brain development. Knowledge of the ODDD gene increases our understanding of the normal process of craniofacial development, as well as of other development pathways.
