T-box transcription factor TBX1 also known asT-box protein 1 andtestis-specific T-box protein is aprotein that in humans is encoded by theTBX1gene.[5] Genes in theT-box family are transcription factors that play important roles in the formation of tissues and organs during embryonic development.[6] To carry out these roles, proteins made by this gene family bind to specific areas ofDNA called T-box binding element (TBE)[6] to control the expression of target genes.
The T-box 1 protein appears to be necessary for the normal development of large arteries that carry blood out of theheart,muscles andbones of the face and neck, and glands such as thethymus andparathyroid.[7][8] Although the T-box 1 protein acts as a transcription factor, it is not yet known which genes are regulated by the protein.
TBX1 is thought to operate on the same developmental pathway asCHD7 which can be mutated inCHARGE syndrome.[9]
Most cases of22q11.2 deletion syndrome are caused by the deletion of a small piece ofchromosome 22. This region of the chromosome contains about 30genes, including theTBX1 gene. In a small number of affected individuals without a chromosome 22 deletion,mutations in theTBX1 gene are thought to be responsible for the characteristic signs and symptoms of the syndrome. Of the three known mutations, two mutations change oneamino acid (a building block of proteins) in the T-box 1 protein. The third mutation deletes a single amino acid from the protein. These mutations likely disrupt the ability of the T-box 1 protein to bind to DNA and regulate the activity of other genes.[10][11][12]
Loss of theTBX1 gene, due to either a mutation in the gene or a deletion of part of chromosome 22, is responsible for many of the features of 22q11.2 deletion syndrome. Specifically, a loss of theTBX1 gene is associated with heart defects, an opening in the roof of the mouth (acleft palate), distinctive facial features, and low calcium levels, but does not appear to cause learning disabilities.[13][14]
^abBollag RJ, Siegfried Z, Cebra-Thomas JA, Garvey N, Davison EM, Silver LM (July 1994). "An ancient family of embryonically expressed mouse genes sharing a conserved protein motif with the T locus".Nature Genetics.7 (3):383–389.doi:10.1038/ng0794-383.PMID7920656.S2CID32296875.
^Jerome LA, Papaioannou VE (March 2001). "DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1".Nature Genetics.27 (3):286–291.doi:10.1038/85845.PMID11242110.S2CID21030663.
^Yamagishi H, Srivastava D (September 2003). "Unraveling the genetic and developmental mysteries of 22q11 deletion syndrome".Trends in Molecular Medicine.9 (9):383–389.doi:10.1016/S1471-4914(03)00141-2.PMID13129704.
^Zhang Y, Han Q, Li C, Li W, Fan H, Xing Q, Yan B (February 2014). "Genetic analysis of the TBX1 gene promoter in indirect inguinal hernia".Gene.535 (2):290–293.doi:10.1016/j.gene.2013.11.012.PMID24295890.
