title: Novel missense mutations and a 288-bp exonic insertion in PAX9 in families with autosomal dominant hypodontia.
abstract: We describe the molecular analysis of three families with hypodontia involving primarily molar teeth and report two novel mutational mechanisms. Linkage analysis of two large families revealed that the hypodontia was linked to the PAX9 locus. These two families revealed missense mutations consisting of a glutamic acid substitution for lysine and a proline substitution for leucine within the paired domain of PAX9. A pair of identical twins affected with hypodontia in a third family demonstrated a 288-bp insertion within exon 2 that resulted in a putative frameshift mutation and a premature stop codon. The insertion was associated with the loss of 7-bp from exon 2. A block of 256-bp of sequence within the insertion was completely identical to downstream sequence from the second intron of the PAX9 gene. These studies extend the spectrum of mutations in PAX9 associated with hypodontia to include heretofore undescribed categories, including missense mutations.
authors.affiliation: Department of Neurology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: Parimal
authors.initials: P
authors.lastname: Das
authors.forename: Mehreen
authors.initials: M
authors.lastname: Hai
authors.forename: Claire
authors.initials: C
authors.lastname: Elcock
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Leal
authors.forename: Donald T
authors.initials: DT
authors.lastname: Brown
authors.forename: Alan H
authors.initials: AH
authors.lastname: Brook
authors.forename: Pragna I
authors.initials: PI
authors.lastname: Patel
mesh_terms: D000595:Amino Acid Sequence; D000848:Anodontia / Q000235:genetics*; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D051764:PAX9 Transcription Factor; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D051764:PAX9 Transcription Factor; C497323:PAX9 protein, human; D014157:Transcription Factors