T-box transcription factor TBX1 also known as T-box protein 1 and testis-specific T-box protein is a protein that in humans is encoded by the TBX1 gene. [5] Genes in the T-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 of DNA called T-box binding element (TBE) [6] to control the expression of target genes.
The TBX1 gene is located on the long (q) arm of chromosome 22 at position 11.21, from base pair 18,118,779 to base pair 18,145,669. [5]
The T-box 1 protein appears to be necessary for the normal development of large arteries that carry blood out of the heart, muscles and bones of the face and neck, and glands such as the thymus and parathyroid. [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 as CHD7 which can be mutated in CHARGE syndrome. [9]
Most cases of 22q11.2 deletion syndrome are caused by the deletion of a small piece of chromosome 22. This region of the chromosome contains about 30 genes, including the TBX1 gene. In a small number of affected individuals without a chromosome 22 deletion, mutations in the TBX1 gene are thought to be responsible for the characteristic signs and symptoms of the syndrome. Of the three known mutations, two mutations change one amino 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 the TBX1 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 the TBX1 gene is associated with heart defects, an opening in the roof of the mouth (a cleft palate), distinctive facial features, and low calcium levels, but does not appear to cause learning disabilities. [13] [14]
Sex-determining region Y protein (SRY), or testis-determining factor (TDF), is a DNA-binding protein encoded by the SRY gene that is responsible for the initiation of male sex determination in therian mammals. SRY is an intronless sex-determining gene on the Y chromosome. Mutations in this gene lead to a range of disorders of sex development with varying effects on an individual's phenotype and genotype.
Twist-related protein 1 (TWIST1) also known as class A basic helix–loop–helix protein 38 (bHLHa38) is a basic helix-loop-helix transcription factor that in humans is encoded by the TWIST1 gene.
Transcription factor 4 (TCF-4) also known as immunoglobulin transcription factor 2 (ITF-2) is a protein that in humans is encoded by the TCF4 gene located on chromosome 18q21.2.
LIM homeobox transcription factor 1-beta, also known as LMX1B, is a protein which in humans is encoded by the LMX1B gene.
Zinc finger E-box-binding homeobox 2 is a protein that in humans is encoded by the ZEB2 gene. The ZEB2 protein is a transcription factor that plays a role in the transforming growth factor β (TGFβ) signaling pathways that are essential during early fetal development.
Zinc finger transcription factor Trps1 is a protein that in humans is encoded by the TRPS1 gene.
DNA polymerase subunit gamma is an enzyme that in humans is encoded by the POLG gene. Mitochondrial DNA polymerase is heterotrimeric, consisting of a homodimer of accessory subunits plus a catalytic subunit. The protein encoded by this gene is the catalytic subunit of mitochondrial DNA polymerase. Defects in this gene are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1), sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome (AHS), and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE).
Forkhead box C1, also known as FOXC1, is a protein which in humans is encoded by the FOXC1 gene.
T-box transcription factor TBX5, is a protein that in humans is encoded by the TBX5 gene. Abnormalities in the TBX5 gene can result in altered limb development, Holt-Oram syndrome, Tetra-amelia syndrome, and cardiac and skeletal problems.
Homeobox protein Hox-A13 is a protein that in humans is encoded by the HOXA13 gene.
Sal-like 1 (Drosophila), also known as SALL1, is a protein which in humans is encoded by the SALL1 gene. As the full name suggests, it is one of the human versions of the spalt (sal) gene known in Drosophila.
Paired-like homeodomain 1 is a protein that in humans is encoded by the PITX1 gene.
Transcription factor SOX-18 is a protein that in humans is encoded by the SOX18 gene.
Paired box protein Pax-1 is a protein that in humans is encoded by the PAX1 gene.
POU domain, class 3, transcription factor 4 is a protein that in humans is encoded by the POU3F4 gene found on the X chromosome.
Transcription factor SOX-14 is a protein that in humans is encoded by the SOX14 gene.
Leucine-zipper-like transcriptional regulator 1 is a protein that in humans is encoded by the LZTR1 gene.
Transport and golgi organization 2 homolog (TANGO2) also known as chromosome 22 open reading frame 25 (C22orf25) is a protein that in humans is encoded by the TANGO2 gene.
Genocopy is a trait that is a phenotypic copy of a genetic trait but is caused by a different genotype. When a genetic mutation or genotype in one locus results in a phenotype similar to one that is known to be caused by another mutation or genotype in another locus, it is said to be a genocopy. However, genocopies may also be referred to as "genetic mimics", in which the same mutation or specific genotype can result in two unique phenotypes in two different patients. The term “Genocopy” was coined by Dr. H. Nachstheim in 1957, in which he discusses “false” phenocopies. In comparison to when a phenotype is the result of an environmental condition that had the same effect as a previously known genetic factor such as mutation. While offspring may inherit specific mutations or genotypes that result in genocopies, phenocopies are not heritable. Two types of elliptocytosis that are genocopies of each other, but are distinguished by the fact that one is linked to the Rh blood group locus and the other is not. The way to distinguish a recessive genocopy from a phenotype caused by a different allele would be by carrying out a test cross, breeding the two together, if they F1 hybrid segregates 1:2:1 then we can determine that it was a genocopy.
DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facial features, frequent infections, developmental delay, intellectual disability and cleft palate. Associated conditions include kidney problems, schizophrenia, hearing loss and autoimmune disorders such as rheumatoid arthritis or Graves' disease.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
