Region Jnkpings ln Odontologiska Institutionen

Isolated Oligodontia Associated with Mutations in EDARADD, AXIN2, MSX1, and PAX9 genes

Bergendal B*, Stecksén-Blicks C, Norderyd J, Dahl N


The aim of the present study was to investigate a cohort of young, unrelated individuals with isolated oligodontia for the prevalence of mutations in the AXIN2, MSX1, PAX9, EDA, and EDAR genes as well as in the novel candidate gene EDARADD. We also searched for genotype-phenotype correlations in carriers of mutations.

Material and Methods

Individuals with isolated oligodontia, defined as a congenital lack of six or more permanent teeth excluding third molars, were asked to participate. The individuals were born 1981–1994 and they originated from three counties in south-east Sweden. The cohort of 93 probands included 40 males (43.0%) and 53 females (57.0%) with a mean of 7.9 congenitally missing teeth (range 6–18).
Peripheral blood samples were collected from all individuals with oligodontia, and genomic DNA was extracted from peripheral nucleated cells using standard techniques. Amplicons for denaturing gradient gel electrophoresis (DGGE) and DNA sequence analysis were generated by hot-start PCR. All variants identified were compared with sequences in the databases NCBI (, Human Gene Mutation Database (, the Biobase ( and with the sequences from all chromosomes included in this cohort in order to exclude polymorphisms.


Mutation screening of all coding sequences of the six genes in 93 individuals revealed sequence alterations predicted to be damaging or potentially damaging in 14 individuals (15.1%): 7 girls and 7 boys. Four mutations were identified in each of the AXIN2, MSX1, and PAX9 genes, respectively. In addition, two probands were identified with mutations in the EDARADD gene. No mutation was found in the EDA or EDAR genes. With the exception of the c.1994dupG mutation in AXIN2, 13 of the 14 mutations are novel. In total, 122 teeth were missing in the 14 probands with mutations, 69 (56.6%) in the maxilla and 53 (43.4%) in the mandible. Their mean number of missing teeth was 8.7 (range 6–18) compared to 7.7 (range 6-16) in the non-mutant group (p>0.05). There was a considerable overlap between mutant gene and patterns of missing teeth.


We found that 15% of probands with isolated oligodontia in an unselected cohort of 93 individuals are associated with primarily novel mutations in the coding regions of four genes: AXIN2, MSX1, PAX9, and EDARADD. This is the first report of mutations in EDARADD associated with isolated oligodontia. Our findings support an extensive genetic heterogeneity behind oligodontia, and we found no evidence for any specific genotype-phenotype correlations.

Uppdaterad: 2013-04-03
Anna Thofelt, Avdelningen för odontologisk radiologi Jönköping, Folktandvården