TBX22 - Clinical Significance

Clinical Significance

In humans, two T-box genes are involved in inherited disorders: mutations in TBX5 cause Holt–Oram syndrome, whereas mutations in TBX3 cause ulnar–mammary syndrome.

Mutations in TBX22 cause X-linked cleft palate and ankyloglossia. CPX has been described in a small number of families exhibiting a strong X linked Mendelian inheritance. The cleft phenotype 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 during palatogenesis, 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.

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. To date, 10 different TBX22 mutations have been reported in patients with CP and/or ankyloglossia. These include small deletions/insertions, nonsense, splice site, frameshift and missense alterations.