TBX22
Encyclopedia
T-box transcription factor TBX22 is a protein
that in humans is encoded by the TBX22 gene
.
TBX22 is a member of a phylogenetically conserved family of proteins that share a common DNA-binding domain, the T-box
. T-box genes encode transcription factor
s involved in the regulation of developmental processes. Mutations in this gene have been associated with the inherited X-linked disorder, cleft palate with ankyloglossia
(tongue-tie), and it is believed to play a major role in human palatogenesis.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. TBX22 mutations also result in non-syndromic cleft palate in some populations.
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 its NH2-terminal region which has the unique feature of missing 20 amino-acids relative to the other known T-domains.
(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.
Functional studies have demonstrated that several T-box genes are involved in mesoderm
specification in the developing embryo of mouse or Xenopus
. In mice, the Brachyury gene is expressed in early mesoderm cells and its expression then becomes restricted to the notochord
. The Brachyury protein binds as a dimer to a 20-nucleotide partially palindromic sequence recognized by its T-domain. More generally, T-box genes have been shown to be critical during development for proper morphogenesis
and organogenesis
. Abnormal expression of several T-box genes has been shown to cause developmental anomalies in mouse, Drosophila
or zebrafish.
.
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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the TBX22 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
TBX22 is a member of a phylogenetically conserved family of proteins that share a common DNA-binding domain, the T-box
T-box
T-box refers to a group of transcription factors involved in limb and heart development. In humans and some other animals, defects in the TBX5 gene expression can lead to finger-like thumbs and ventricular septal defects in which there is no separation between the left and right ventricle of the...
. T-box genes encode transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s involved in the regulation of developmental processes. Mutations in this gene have been associated with the inherited X-linked disorder, cleft palate with ankyloglossia
Ankyloglossia
Ankyloglossia, commonly known as tongue tied, is a congenital oral anomaly which may decrease mobility of the tongue tip and is caused by an unusually short, thick lingual frenulum, a membrane connecting the underside of the tongue to the floor of the mouth...
(tongue-tie), and it is believed to play a major role in human palatogenesis.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. TBX22 mutations also result in non-syndromic cleft palate in some populations.
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 its NH2-terminal region which has the unique feature of missing 20 amino-acids relative to the other known T-domains.
Function
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 mouse BrachyuryBrachyury
Brachyury is a protein that in humans is encoded by the T gene. Brachyury is a transcription factor within the T-box complex of genes. It has been found in all bilaterian animals that have been screened, and is also present in the cnidaria.-History:...
(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.
Functional studies have demonstrated that several T-box genes are involved in mesoderm
Mesoderm
In all bilaterian animals, the mesoderm is one of the three primary germ cell layers in the very early embryo. The other two layers are the ectoderm and endoderm , with the mesoderm as the middle layer between them.The mesoderm forms mesenchyme , mesothelium, non-epithelial blood corpuscles and...
specification in the developing embryo of mouse or Xenopus
Xenopus
Xenopus is a genus of highly aquatic frogs native to Sub-Saharan Africa. There are 19 species in the Xenopus genus...
. In mice, the Brachyury gene is expressed in early mesoderm cells and its expression then becomes restricted to the notochord
Notochord
The notochord is a flexible, rod-shaped body found in embryos of all chordates. It is composed of cells derived from the mesoderm and defines the primitive axis of the embryo. In some chordates, it persists throughout life as the main axial support of the body, while in most vertebrates it becomes...
. The Brachyury protein binds as a dimer to a 20-nucleotide partially palindromic sequence recognized by its T-domain. More generally, T-box genes have been shown to be critical during development for proper morphogenesis
Morphogenesis
Morphogenesis , is the biological process that causes an organism to develop its shape...
and organogenesis
Organogenesis
In animal development, organogenesis is the process by which the ectoderm, endoderm, and mesoderm develop into the internal organs of the organism. Internal organs initiate development in humans within the 3rd to 8th weeks in utero...
. Abnormal expression of several T-box genes has been shown to cause developmental anomalies in mouse, Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
or zebrafish.
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 syndromeUlnar–mammary syndrome
Ulnar–mammary syndrome is a cutaneous condition characterized by nipple and breast hypoplasia or aplasia.It has been associated with TBX3.- References :...
.
CPX has been described in a small number of families exhibiting a strong X linked Mendelian inheritance. The cleft phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
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.