TBX22
   HOME

TheInfoList



OR:

T-box transcription factor TBX22 is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''TBX22''
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. 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 In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
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.


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 Brachyury (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 The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical E ...
specification in the developing embryo of mouse or ''
Xenopus ''Xenopus'' () (Gk., ξενος, ''xenos''=strange, πους, ''pous''=foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-known ...
''. In mice, the Brachyury gene is expressed in early mesoderm cells and its expression then becomes restricted to the
notochord In anatomy, the notochord is a flexible rod which is similar in structure to the stiffer cartilage. If a species has a notochord at any stage of its life cycle (along with 4 other features), it is, by definition, a chordate. The notochord consis ...
. 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 ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
'' or zebrafish.


Clinical significance

In humans, two T-box genes are involved in inherited disorders: mutations in TBX5 cause
Holt–Oram syndrome Holt–Oram syndrome (also called atrio-digital syndrome, atriodigital dysplasia, cardiac-limb syndrome, heart-hand syndrome type 1, HOS, ventriculo-radial syndrome) is an autosomal dominant disorder that affects bones in the arms and hands (the ...
, whereas mutations in TBX3 cause
ulnar–mammary syndrome Ulnar–mammary syndrome or Schinzel syndrome is a cutaneous condition characterized by micromastia, nipple and breast hypoplasia or aplasia. Features of UMS can be mild to severe and can vary significantly from person to person, even within the s ...
. 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 In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
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.


References


Further reading

* * * * * * * * * * *


External links

*
WikiGenes TBX22
* * {{Transcription factors, g4 Transcription factors