Humans ; Anodontia/genetics* ; Tooth Abnormalities/genetics* ; Mutation ; Malocclusion/genetics* ; Wnt Proteins/genetics*

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

Tooth agenesis is the most common form of congenital craniofacial dysplasia seen in stomatology clinics, which may be caused by genetic and/or environmental factors. Tooth development is regulated by a series of signaling pathways, and variants in any of these strictly balanced signaling cascades can result in tooth agenesis and/or other oral defects. Notably, variants of genes of the Wnt/beta-catenin signaling pathway are important cause for both non-syndromic and syndromic tooth agenesis. This article has provided a review for the molecular genetics of tooth agenesis associated with Wnt/beta-catenin signaling pathway, which may shed lights on the etiology and molecular mechanism of this disease.
Anodontia/genetics* ; Genetic Research ; Humans ; Tooth ; Wnt Proteins/genetics* ; Wnt Signaling Pathway/genetics*

The goal of this study was to identify MSX1 gene variants in multiple Chinese families with nonsyndromic oligodontia and analyse the functional influence of these variants. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variants in five families with nonsyndromic oligodontia, and a series of bioinformatics databases were used for variant confirmation and functional prediction. Phenotypic characterization of the members of these families was described, and an in vitro analysis was performed for functional evaluation. Five novel MSX1 heterozygous variants were identified: three missense variants [c.662A>C (p.Q221P), c.670C>T (p.R224C), and c.809C>T (p.S270L)], one nonsense variant [c.364G>T (p.G122*)], and one frameshift variant [c.277delG (p.A93Rfs*67)]. Preliminary in vitro studies demonstrated that the subcellular localization of MSX1 was abnormal with the p.Q221P, p.R224C, p.G122*, and p.A93Rfs*67 variants compared to the wild type. Three variants (p.Q221P, p.G122*, and p.A93Rfs*67) were classified as pathogenic or likely pathogenic, while p.S270L and p.R224C were of uncertain significance in the current data. Moreover, we summarized and analysed the MSX1-related tooth agenesis positions and found that the type and variant locus were not related to the severity of tooth loss. Our results expand the variant spectrum of nonsyndromic oligodontia and provide valuable information for genetic counselling.
Anodontia/genetics* ; Humans ; MSX1 Transcription Factor/genetics* ; Pedigree ; Whole Exome Sequencing

Anodontia ; classification ; epidemiology ; etiology ; genetics ; Genetic Diseases, X-Linked ; etiology ; genetics ; Humans ; Mutation ; Prevalence ; Tooth Abnormalities ; etiology ; genetics

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

A case of hypohidrotic ectodermal dysplasia was seen at the Dermatological Clinic of Chosun Univeraity Hospital, with a classical symptom triad consisting of hypohidrosis to anhidroais, hypotrichosis and hypodontia, and characteristic facial appearance. He was a 20 year-old male patient who presented, in addition, milium-like papules of sebaceous hyperplasia located on the nose and cheeks, supernumerary nipples of right breast, ceruminosis since childhood, and absence of apocrine glands on the axilla and pubic area, all of which are not frequently observed in hypohidrotic ectodermal dysplasia. Dermatoglyphics of this patient revealed that the axial triradius of the left palm was t, its atd angle was 42 degree, and the total ridge count of finger print was 5. This patient has no relatives showing the symptoms of hypohidrotic ectodermal dysplasia and the genetics was discussed in relation to this disease.
Anodontia ; Apocrine Glands ; Axilla ; Breast ; Cheek ; Dermatoglyphics ; Ectodermal Dysplasia 1, Anhidrotic* ; Fingers ; Genetics ; Humans ; Hyperplasia ; Hypohidrosis ; Hypotrichosis ; Male ; Nipples ; Nose ; Young Adult

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

OBJECTIVETo study the relationships between single nucleotide polymorphisms (SNP) of gene msh homebox-1 (MSX-1) (rs3821949, rs12532) and sporadic tooth agenesis by filtering the susceptibility genes in a Jiangsu province population.

METHODSDNA samples were extracted from 198 patients with sporadic tooth agenesis and 207 control subjects. Two MSX-1 gene polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The association between the genetic polymorphism and risk of sporadic tooth agenesis was estimated by chi(2) and logistic regression. The Phase was used to determine the Hardy-Weinberg equilibrium and haplotype association.

RESULTSIn the population, the allele frequency and genotype rates of the SNP rs3821949 were significant different between the patients with sporadic tooth agenesis and normal controls: the A allele frequency in the patients (43.2%) was significantly higher than that in the normal controls (31.4%, P = 0.008), and the AA genotype rate of the patients (14.7%) was significantly higher than that of the controls (12.6%, P = 0.030). However, There were no significant differences in the allele frequency and genotype rates of the SNP rs12532 between the patients with sporadic tooth agenesis and normal controls. Similar results were obtained between the mandibular incisor agenesis cases and controls. The haplotype frequencies of GA (27.9%) were significantly lower in non-mandibular incisor agenesis cases group than that in the control group (37.0%, P = 0.03, OR = 0.51).

CONCLUSIONSThe results show that SNP rs3821949, which is located at 5';near region of the MSX-1 gene, is likely to have an influence on the transcriptional activity of this gene and be associated with sporadic tooth agenesis. The haplotypes constructed with these 2 SNP sites may be linked with the susceptibility gene of non-mandibular incisor agenesis.

Adolescent ; Adult ; Anodontia ; genetics ; Case-Control Studies ; Child ; China ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Incisor ; abnormalities ; MSX1 Transcription Factor ; genetics ; Male ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Young Adult