Development of Gene diagnosis of Oral-Maxillofacial Deseases by Saliva-derived DNA

受体的突变与越来越多的影响口腔-颅面功能的遗传性人类疾病综合征有关。在本研究中，我们分析了与遗传性综合征(新生基底细胞癌综合征；采用聚合酶链式反应-单链构象多态性分析和外周血淋巴细胞及唾液DNA直接测序的方法，检测各证型与各证型的表型/基因相关性。此外，我们还研究了表达突变基因的靶细胞的细胞生长、分化和细胞内信号转导途径，以阐明突变受体基因在综合征中的分子功能。我们描述了疾病突变的分子后果，并预测还有许多新的突变有待鉴定。

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.