Cleft lip with cleft palate, ankyloglossia, and hypodontia are associated with TBX22 mutations.
X-linked cleft palate and ankyloglossia (CPX) are caused by mutations in the TBX22 transcription factor. To investigate whether patients with ankyloglossia alone or in the presence of other craniofacial features including hypodontia or CLP might be caused by TBX22 mutations, we analyzed 45 Thai patients with isolated ankyloglossia, 2 unusual CPA families, and 282 non-syndromic Thai and UK patients with CLP. Five putative missense mutations were identified, including 3 located in the T-box binding domain (R120Q, R126W, and R151L) that affects DNA binding and/or transcriptional repression. The 2 novel C-terminal mutations, P389Q and S400Y, did not affect TBX22 activity. Mutations R120Q and P389Q were identified in patients with ankyloglossia only, while R126W and R151L were present in families that included CLP. Several individuals in these families were also found to have micro/hypodontia. This study has expanded the phenotypic spectrum of TBX22-related mutations to include dental anomalies and cleft lip.
Department of Orthodontics and Paediatric Dentistry, and Craniofacial Genetics Laboratory, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
P N
PN
Kantaputra
M
M
Paramee
A
A
Kaewkhampa
A
A
Hoshino
M
M
Lees
M
M
McEntagart
N
N
Masrour
G E
GE
Moore
E
E
Pauws
P
P
Stanier
D000293:Adolescent; D000848:Anodontia / Q000235:genetics*; D001120:Arginine / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D015331:Cohort Studies; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007742:Labial Frenum / Q000002:abnormalities*; D007930:Leucine / Q000235:genetics; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D011392:Proline / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012694:Serine / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics*; D014060:Tongue Diseases / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D014364:Tryptophan / Q000235:genetics; D014443:Tyrosine / Q000235:genetics
D004268:DNA-Binding Proteins; D020825:T-Box Domain Proteins; C416943:TBX22 protein, human; D005973:Glutamine; D014443:Tyrosine; D012694:Serine; D014364:Tryptophan; D001120:Arginine; D011392:Proline; D007930:Leucine