Novel mutations of PAX9 gene in Chinese patients with oligodontia / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the mutational characteristics of PAX9 gene in Chinese patients with congenital oligodontia and thus to provide a molecular basis for studying the pathogenesis of oligodontia.</p><p><b>METHODS</b>Thirteen individuals with oligodontia and 9 healthy individuals, from 4 unrelated autosomal dominant families, and 16 sporadic patients with hypodontia in China, as well as 196 healthy control individuals (without oligodontia or hypodontia) were screened. Congenital absence of teeth was confirmed by panoramic X-ray analysis. Mutations of PAX9 gene were detected using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. After the finding of abnormal SSCP bands, analysis was carried out with DNA sequencing.</p><p><b>RESULTS</b>PCR-SSCP detected SSCP bands alteration in exon2 of PAX9 gene in two unrelated families. Sequencing of PAX9 gene revealed a novel frameshift mutation (109InsG) and a novel missense mutation (C139T). All the affected members of each family were heterozygous for the mutations. In sporadic patients and the other two families, no similar sequence changes in PAX9 gene were found.</p><p><b>CONCLUSIONS</b>The results extend the spectrum of mutations in PAX9 gene associated with oligodontia. The novel mutations will play an important role in gene diagnosis of oligodontia.</p>

Functional analysis of novel mutations in PAX9 associated with familial oligodontia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To gain new insights into the molecular pathogenesis of the 109(InsG) and 139(C--> T) mutations and their roles in familial oligodontia.</p><p><b>METHODS</b>The region of PAX9 paired domain (PAX9PD) was amplified and the expression plasmids were constructed in pGEXlambda -1T by PCR-based cloning. PAX9PD proteins were prepared on the basis of GST instruction. The binding of wild type and two novely mutant PAX9 paired domain to double-stranded DNA targets were analyzed by gel mobility shift assay.</p><p><b>RESULTS</b>Wild type PAX9PD protein bind to the high affinity paired domain recognition sequences, CD19-2(A-ins) and Pax6CON, the 109(InsG) and 139(C--> T) mutant PAX9PD protein were unable to bind to these cognate DNA-binding sites.</p><p><b>CONCLUSION</b>The functional defects in DNA binding of mutant 109(InsG) PAX9 and 139(C--> T) PAX9, as well as loss-of-function of PAX9 most likely result in its haploinsufficiency during the patterning of dentition and the subsequent loss of posterior teeth.</p>