T-box transcription factor TBX22 is aprotein that in humans is encoded by theTBX22gene.[5]
TBX22 is a member of a phylogenetically conserved family of proteins that share a common DNA-binding domain, theT-box. T-box genes encodetranscription factors involved in the regulation of developmental processes. Mutations in this gene have been associated with the inherited X-linked disorder,cleft palate withankyloglossia (tongue-tie), and it is believed to play a major role in human palatogenesis.[5] It has previously been mapped to the long arm of the X chromosome and it has now been demonstrated that mutations in the gene TBX22 are the cause of this syndrome.[6] TBX22 mutations also result in non-syndromiccleft palate in some populations.[7]
TBX22 is composed of seven exons spanning 8.7 kilobases of genomic DNA in Xq21.1. The TBX22 mRNA is 2099 base pairs long and encodes a 400-amino-acids protein containing a T-domain in itsNH2-terminal region which has the unique feature of missing 20 amino-acids relative to the other known T-domains.[8]
T-box genes are members of a family of transcriptional regulators that contain a region encoding a conserved DNA-binding motif of approximately 200 amino acids: the T-domain. These genes are grouped together on the basis of the homology existing between their products and the mouseBrachyury (or T) protein. In human and mouse, numerous T-domain-containing genes have been identified so far and mapped throughout the genome. The spatio-temporal expression of these genes is strictly regulated during the development of both vertebrates and invertebrates.[8]
Functional studies have demonstrated that several T-box genes are involved inmesoderm specification in the developing embryo of mouse orXenopus. In mice, the Brachyury gene is expressed in early mesoderm cells and its expression then becomes restricted to thenotochord. The Brachyury protein binds as a dimer to a 20-nucleotide partiallypalindromic sequence recognized by its T-domain. More generally, T-box genes have been shown to be critical during development for propermorphogenesis andorganogenesis. Abnormal expression of several T-box genes has been shown to cause developmental anomalies in mouse,Drosophila or zebrafish.
TBX22 mutations in two families predicted to have X linked cleft palate and ankyloglossia. Sequence electropherograms from genomic DNA amplified from exon 5 (family K) and exon 4 (family W) are of affected (mutant) males and unaffected (control) females. *Represents the site of the sequence variant.
Mutations in TBX22 cause X-linked cleft palate and ankyloglossia.[9] CPX has been described in a small number of families exhibiting a strong X linked Mendelian inheritance. The cleftphenotype predominantly affects males who show variation ranging from a complete cleft of the secondary palate, submucous cleft, or bifid uvula to high arched palate. Ankyloglossia is frequently seen in affected patients and carrier females, and has proved to be a useful indicator of CPX. Temporal and spatial studies using in situ hybridization in both human and mouse has shown that TBX22/Tbx22 is expressed primarily in the palatal shelves and tongue duringpalatogenesis, indicating a specific role of TBX22 in both palatal and tongue development. In addition to families with well defined X linked inheritance, TBX22 mutations have been identified in several families where pedigree size and/or family history were too limited to predict mode of inheritance. In these cases, ascertainment was largely based on the presence of ankyloglossia as well as cleft palate.[10]
It has been demonstrated that TBX22 makes a significant contribution to the prevalence of cleft palate at least in the Brazilian and the North American cohorts.[8] To date, 10 different TBX22 mutations have been reported in patients with CP and/or ankyloglossia.[11] These include small deletions/insertions, nonsense, splice site, frameshift and missense alterations.[7]
^Braybrook C, Doudney K, Marçano AC, et al. (2001). "The T-box transcription factor gene TBX22 is mutated in X-linked cleft palate and ankyloglossia".Nat. Genet.29 (2):179–83.doi:10.1038/ng730.PMID11559848.S2CID28939959.
^abcdLaugier-Anfossi F, Villard L (2000). "Molecular characterization of a new human T-box gene (TBX22) located in xq21.1 encoding a protein containing a truncated T-domain".Gene.255 (2):289–96.doi:10.1016/S0378-1119(00)00326-7.PMID11024289.
Laugier-Anfossi F, Villard L (2000). "Molecular characterization of a new human T-box gene (TBX22) located in xq21.1 encoding a protein containing a truncated T-domain".Gene.255 (2):289–96.doi:10.1016/S0378-1119(00)00326-7.PMID11024289.
Braybrook C, Doudney K, Marçano AC, et al. (2001). "The T-box transcription factor gene TBX22 is mutated in X-linked cleft palate and ankyloglossia".Nat. Genet.29 (2):179–83.doi:10.1038/ng730.PMID11559848.S2CID28939959.
