title: Craniofacial expression of human and murine TBX22 correlates with the cleft palate and ankyloglossia phenotype observed in CPX patients.
abstract: Cleft palate with ankyloglossia (CPX; MIM 303400) is inherited as a Mendelian, semidominant X-linked disorder and has been described in several large families from different ethnic origins. It is a useful genetic model for non-syndromic cleft palate, a common congenital disorder. Recently, the underlying genetic defect in CPX was identified, where unique mutations were found in the T-box-containing transcription factor TBX22. Here we report two new familial cases with novel missense and insertion mutations, each occurring within the T-box domain and highlighting the functional significance of this DNA-binding motif. We describe TBX22 expression in early human development, where expression is found in the palatal shelves and is highest prior to elevation to a horizontal position above the tongue. mRNA is also detected in the base of the tongue in the region of the frenulum that corresponds to the ankyloglossia seen in CPX patients. Other sites of expression include the inferior portion of the nasal septum that fuses to the palatal shelves, the mesenchyme from which tooth buds develop, and the tooth buds themselves. We have also identified the orthologous mouse Tbx22 gene and performed expression analysis in E12.5-E17.5 mouse embryos. The location of mRNA expression closely correlates between mouse and human, while at later stages of development, we also detected expression in mouse lung and whisker follicles. We conclude that expression of TBX22 is entirely consistent with the CPX phenotype and that the mouse should provide a useful model for elucidating its role in craniofacial development.
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College Faculty of Medicine-Hammersmith Campus, Du Cane Road, London W12 ONN, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Braybrook
authors.forename: Steven
authors.initials: S
authors.lastname: Lisgo
authors.forename: Kit
authors.initials: K
authors.lastname: Doudney
authors.forename: Deborah
authors.initials: D
authors.lastname: Henderson
authors.forename: Ana Carolina B
authors.initials: AC
authors.lastname: Marçano
authors.forename: Tom
authors.initials: T
authors.lastname: Strachan
authors.forename: Michael A
authors.initials: MA
authors.lastname: Patton
authors.forename: Laurent
authors.initials: L
authors.lastname: Villard
authors.forename: Gudrun E
authors.initials: GE
authors.lastname: Moore
authors.forename: Philip
authors.initials: P
authors.lastname: Stanier
authors.forename: Susan
authors.initials: S
authors.lastname: Lindsay
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002972:Cleft Palate / Q000196:embryology / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008035:Lingual Frenum / Q000002:abnormalities* / Q000196:embryology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D020825:T-Box Domain Proteins / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D020825:T-Box Domain Proteins; C416943:TBX22 protein, human; C534956:Tbx22 protein, mouse; D004247:DNA