A missense mutation in PAX9 in a family with distinct phenotype of oligodontia.
Mutations in PAX9 have been described for families in which inherited oligodontia characteristically involves permanent molars. Our study analysed one large family with dominantly inherited oligodontia clinically and genetically. In addition to permanent molars, some teeth were congenitally missing in the premolar, canine, and incisor regions. Measurements of tooth size revealed the reduced size of the proband's and his father's deciduous and permanent teeth. This phenotype is distinct from oligodontia phenotypes associated with mutations in PAX9. Sequencing of the PAX9 gene revealed a missense mutation in the beginning of the paired domain of the molecule, an arginine-to-tryptophan amino-acid change occurring in a position absolutely conserved in all sequenced paired box genes. A mutation of the homologous arginine of PAX6 has been shown to affect the target DNA specificity of PAX6. We suggest that a similar mechanism explains these distinct oligodontia phenotypes.
Lammi
Laura
L
Institute of Dentistry, University of Helsinki, Finland. laura.lammi@helsinki.fi
Halonen
Katri
K
Pirinen
Sinikka
S
Thesleff
Irma
I
Arte
Sirpa
S
Nieminen
Pekka
P
D000595:Amino Acid Sequence; D000848:Anodontia / Q000000981:diagnostic imaging / Q000235:genetics*; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008963:Molar; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D051764:PAX9 Transcription Factor; D010375:Pedigree; D010641:Phenotype; D011859:Radiography; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014070:Tooth / Q000000981:diagnostic imaging; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D051764:PAX9 Transcription Factor; C497323:PAX9 protein, human; D014157:Transcription Factors