| Research Abstract |
Mutations in receptors have been linked to an increasing number of inherited human disease syndromes affecting oral-craniofacial functions. Both gain-of-function mutations resulting in constitutive receptor activation, and loss-of-function mutations resulting in non-functional or dominant negative receptors, have been observed.
In the present study, we have analyzed the mutations of receptor families (patched ; a receptor for the hedgehog protein, fibroblast growth factor receptor (FGFR)-1, -2, -3, Tie-2 ; an endothelial cell-specific receptor tyrosine kinase) that are involved in inherited syndromes (nevoid basal cell carcinoma syndrome ; NBCCS/Gorlin Syndrome, craniosynostosis, achondroplasia, oral cancers and venous malformations, respectively) by both PCR-SSCP and direct sequencing of the DNA derived from peripheral blood lymphocytes and saliva, to examine the phenotype/genotype correlations in patients with the syndromes. In addition, we have studied cellular growth, differentiation and intracellular signal transduction pathways in the target cells expressing mutated genes to elucidate the molecular function of the mutated receptor genes in the syndromes.
We describes the molecular consequences of the disease mutations, and predicts that many novel mutations remain to be identified.
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