OBJECTIVETo analyze the correlation between the phenotype and genotype of tooth agenesis using the tooth agenesis code (TAC) and the traditional descriptor for missing teeth.

METHODSPatients with isolated hypodontia caused by PAX9 or MSX1 mutation reported before May 2007 were enrolled. The teeth missing rate and TAC code were recorded. The missing teeth patterns caused by the two mutations were compared.

RESULTSThe teeth missing rates in each teeth positions were significantly different between maxillary and mandibular except maxillary central incisor, lateral incisor and mandibular canine, first molar (P<0.05, P<0.001). MSX1 gene mutation often led to the loss of maxillary first premolar, maxillary second premolar, and mandibular second premolar, while PAX9 gene mutation often led to the loss of the first, second, and third molars. The results were similar when analyzed either by TAC code analysis or by traditional descriptor.

CONCLUSIONSPAX9 and MSX1 gene mutation can cause different phenotypes of tooth agenesis. The TAC code can be used in the analysis of the correlation between phenotype and genotype of the missing teeth patients.

Anodontia ; genetics ; Genotype ; Humans ; MSX1 Transcription Factor ; genetics ; Mutation ; PAX9 Transcription Factor ; genetics ; Phenotype

OBJECTIVETo investigate the mutation characteristics of paired box homeotic gene 9 (PAX9) and muscle segment homeobox gene 1 (MSX1) of patients with congenital oligodontia.

METHODSClinical manifestations were recorded by taking complete oral examinations in patients with congenital nonsyndromic oligodontia and some of his normal family members. Pedigree information was confirmed by extended interviews and a pedigree was constructed. Inheritance mode and clinical features were analyzed. Assessment of crown width compared to normal value of crown width in Chinese people was based on the registrations and measurements of study cast. Comparison of craniofacial form, malocclusion types and characteristics were conducted via cephalometric analysis by taking lateral cephalometric radiographics. Venous blood samples were collected and DNA was extracted from leukocytes. DNA sequencing and mutation analysis were analyzed in exon 1, 2, 3, 4 of PAX9 and exon 1, 2 of MSX1 coding region by polymerase chain reaction (PCR).

RESULTSThe teeth shape abnormality of the patient was noticed by a measured smaller crown width compared to normal values of crown width in Chinese people. The result of cephalometric analysis indicated no obvious inherited tendency in the proband in terms of facial osseo type and jaw bone pattern. One mutation was found in the proband and his mother in exon 3 of PAX9, the missense mutation G718C causing a conservative change A240P was present. Mutation was not found in MSX1.

CONCLUSIONThese findings suggest that the missense mutation G718C in exon 3 of PAX9 is likely the cause of oligodontia.

Adolescent ; Anodontia ; Asian Continental Ancestry Group ; DNA Mutational Analysis ; Female ; Humans ; Male ; Mutation ; PAX9 Transcription Factor ; Pedigree ; Polymerase Chain Reaction ; Sequence Analysis, DNA

OBJECTIVETo 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.

METHODSThirteen 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.

RESULTSPCR-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.

CONCLUSIONSThe 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.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Child ; Female ; Frameshift Mutation ; Humans ; Male ; Middle Aged ; Mutation, Missense ; PAX9 Transcription Factor ; genetics ; Pedigree ; Tooth Loss ; congenital ; genetics ; Young Adult

OBJECTIVETo gain new insights into the molecular pathogenesis of the 109(InsG) and 139(C--> T) mutations and their roles in familial oligodontia.

METHODSThe 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.

RESULTSWild 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.

CONCLUSIONThe 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.

Anodontia ; genetics ; Base Sequence ; Chromatography, High Pressure Liquid ; DNA Mutational Analysis ; Electrophoretic Mobility Shift Assay ; Family Health ; Humans ; Mutation ; PAX9 Transcription Factor ; genetics ; metabolism ; Polymerase Chain Reaction

Objective To investigate the effects of miR-181b-5p on cells proliferation and apoptosis in acute myeloid leukemia (AML) by targeting paired box 9 (PAX9). Methods The relationship between expression level of PAX9 and prognosis in AML patients was analyzed by gene expression profiling interactive analysis (GEPIA) database and The Cancer Genome Atlas (TCGA) database. Kasumi-1 and AML5 cells were transfected with empty vector (Vector group) or PAX9 (PAX9 group). The proliferation activity was detected by CCK-8 assay, and cells cycle and apoptosis were detected by flow cytometry. Expressions of cyclin-dependent kinase 2 (CDK2), cyclin B1 (CCNB1), B-cell lymphoma 2 (Bcl2) and Bcl2-associated X protein (BAX) were detected by Western blot analysis. The targeted microRNA (miRNA) by PAX9 was predicted by bioinformatics analysis, and the targeted effect was verified by luciferase reporter assay. The level of PAX9 mRNA was detected by real-time quantitative PCR, and expression of PAX9 protein was detected by Western blot analysis. Kasumi-1 and AML5 cells were transfected with miR-NC (miR-NC group) or miR-181b-5p (miR-181b-5p group). The cells were further transfected with PAX9 (miR-181b-5p combined with PAX9 group) in miR-181b-5p group. The proliferation, cycle and apoptosis of cells were detected by the above methods.Results GEPIA and TCGA databases showed that the expression of PAX9 was down-regulated in AML patients, which was correlated with poor prognosis. In Kasumi-1 and AML5 cells, compared with Vector group, proliferation activity of cells, percentage of cells in S phase, and expressions of CDK2, CCNB1 and Bcl2 proteins were decreased, while percentage of cells in G0/G1 phase, apoptosis rate and the expression of BAX protein were increased in PAX9 group. It was confirmed by double luciferase reporter assay that PAX9 was the target gene of miR-181b-5p. Compared with miR-NC group, proliferation activity of cells, percentage of cells in S phase, and expressions of CDK2, CCNB1 and Bcl2 proteins were increased, while percentage of cells in G0/G1 phase, apoptosis rate and the expression of BAX protein were decreased in miR-181b-5p group. Compared with miR-181b-5p group, proliferation activity of cells, percentage of cells in S phase, and expressions of CDK2, CCNB1 and Bcl2 proteins were decreased, while percentage of cells in G0/G1 phase, apoptosis rate and the expression of BAX protein were increased in miR-181b-5p combined with PAX9 group. Conclusion The miR-181b-5p can promote the proliferation of AML cells and delay apoptosis by inhibiting PAX9.
Humans ; Apoptosis/genetics* ; bcl-2-Associated X Protein ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Leukemia, Myeloid, Acute/pathology* ; Luciferases ; MicroRNAs/metabolism* ; PAX9 Transcription Factor/genetics*

OBJECTIVETo investigate the mutation in transcription factor paired box gene PAX9 in a mongolian family with non-syndromic oligodontia.

METHODSPeripheral blood was collected from 17 core family members (9 unaffected, 8 affected) in this Mongolian family with non-syndromic oligodontia. Mutation in exons of PAX9 gene was identified by PCR amplification and DNA sequencing.

RESULTSA point mutation c.87G > C at position 87 in exon 4 of PAX9 was identified from 8 affected members in the family, which were G/C heterozygous.While the 9 healthy members in the family were homozygous for C which was consistent with normal reference sequence in the GenBank(accession number: NC_000014).

CONCLUSIONSThe mutation of c.87G > C (p. Ala240Pro) in exon 4 of PAX9 was likely to cause the non-syndromic oligodontia in this Mongolian family.

Adolescent ; Anodontia ; ethnology ; genetics ; Asian Continental Ancestry Group ; genetics ; DNA ; genetics ; Exons ; Female ; Heterozygote ; Humans ; Male ; Nucleic Acid Amplification Techniques ; PAX9 Transcription Factor ; genetics ; Pedigree ; Point Mutation ; Polymerase Chain Reaction ; Sequence Analysis, DNA