Human Molecular Genetics, 2002, Vol. 11, No. 22 2793-2804
© 2002 Oxford University Press
Craniofacial expression of human and murine TBX22 correlates with the cleft palate and ankyloglossia phenotype observed in CPX patients
1Institute of Reproductive and Developmental Biology, Imperial College Faculty of Medicine–Hammersmith Campus, Du Cane Road, London W12 ONN, UK, 2Institute of Human Genetics, University of Newcastle, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK, 3Medical Genetics Unit, St George's Hospital Medical School, London SW17 0RE, UK and 4INSERM U491, Faculté de Médecine La Timone, Marseille, France
Received July 5, 2002; Accepted August 8, 2002
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.
* To whom correspondence should be addressed Tel: +;44 2075942124; Fax: +;44 2075942129; Email: pstanier{at}ic.ac.uk
The authors wish it to be known what, in their opinion, the first two authors should be regarded as joint First Authors.
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