DEVELOPMENT OF DIAGNOSTIC-TOOLS FOR THE ANALYSIS OF 5P DELETIONS USING INTERPHASE FISH

Cri-du-chat syndrome is associated with a deletion of the short arm of chromosome 5. Through the phenotypic and molecular analyses of indivi duals with a subset of the features associated with the syndrome, the genes involved in the syndrome have been mapped to two distinct critic al regions. Deletion of a critical region in 5p15.2 results in the dis tinct facial features associated with the syndrome as well as the seve re mental and developmental delay, while a deletion of 5p15.3 is assoc iated only with the characteristic cat-like cry, the key diagnostic fe ature of the syndrome. Therefore, subtle differences in the extent of the 5p deletion can have a profound affect on the prognosis of the pat ient. In order to more easily differentiate between deletions that lea d to the cri-du-chat syndrome phenotype and deletions that lead only t o the isolated cat-like cry, we have constructed YAC contigs that span both critical regions. The YAC clones have been used to isolate cosmi ds mapping to each critical region and cosmids that lie just within th e two critical region boundaries have been identified. We report here on the use of these cosmids as probes for fluorescent in situ hybridiz ation experiments on interphase nuclei as a means of more accurately d ifferentiating between small 5p deletions that coincide with a complet e cri-du-chat syndrome phenotype and the severe mental and development al delay that is associated with it and deletions that only delete the distal critical region that coincide with the isolated cat-like cry a nd a much improved prognosis.