A novel nonsense mutation in PAX9 is associated with marked variability in number of missing teeth.
Tooth development is under strict genetic control. During the last decade, studies in molecular genetics have led to the identification of gene defects causing the congenital absence of permanent teeth. Analyses of PAX9 and MSX1 in nine families with hypodontia and oligodontia revealed one new PAX9 mutation. A LOD score of Z = 1.8 (theta = 0.0) was obtained for D14S75 close to PAX9 in one three-generation family, and sequencing of the gene identified the nonsense mutation c.433C>T. The mutation results in a truncated PAX9 protein containing the paired domain region as a result of the Q145X stop mutation. The family showed a marked phenotypic variability in the number of missing teeth, ranging from 2 to 15 missing teeth. The highest frequency of missing teeth was found for second molars followed by second premolars.
Hansen
Lars
L
Department of Cellular and Molecular Medicine and The Wilhelm Johannsen Center for Functional Genome Research, The Panum Insitute, University of Copenhagen, Blegdamsvej 3b, DK 2200 Copenhagen N, Denmark. larsh@imbg.ku.dk
Kreiborg
Sven
S
Jarlov
Henrik
H
Niebuhr
Erik
E
Eiberg
Hans
H
D000848:Anodontia / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics*; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D008126:Lod Score; D051957:MSX1 Transcription Factor / Q000235:genetics*; D051764:PAX9 Transcription Factor / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D017422:Sequence Analysis, DNA
D018389:Codon, Nonsense; D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; D051764:PAX9 Transcription Factor; C497323:PAX9 protein, human; D012333:RNA, Messenger