Saethre-Chotzen syndrome More than 80 mutations in the TWIST1 gene have been identified in people with Saethre-Chotzen syndrome. Some of these mutations change single protein building blocks (amino acids) in the TWIST1 protein, while others delete or insert genetic material in the gene. In some cases, this condition is caused by chromosomal abnormalities (translocations or deletions) involving the region of chromosome 7 that contains the TWIST1 gene. TWIST1 mutations prevent one copy of the gene in each cell from producing any functional protein. A shortage of functional TWIST1 protein affects the development and maturation of cells in the skull, face, and limbs. These abnormalities underlie the signs and symptoms of Saethre-Chotzen syndrome, although it is unclear exactly how a shortage of the TWIST1 protein causes specific features such as the premature fusion of certain skull bones. other disorders TWIST1 mutations have also been found in several people with isolated craniosynostosis, which is a premature fusion of certain skull bones that occurs without the other signs and symptoms of Saethre-Chotzen syndrome. These mutations occur near the end of the gene in a region known as the TWIST box domain. This domain enables the TWIST1 protein to bind to and regulate a gene called RUNX2, which is a critical regulator of bone formation. Researchers believe that mutations in the TWIST box domain prevent the TWIST1 protein from effectively controlling the activity of the RUNX2 gene, which disrupts the normal pattern of bone formation in the skull and leads to craniosynostosis.

     The TWIST1 gene provides instructions for making a protein that plays an important role in early development. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and controls the activity of particular genes. Specifically, the TWIST1 protein is part of a large protein family called basic helix-loop-helix (bHLH) transcription factors. Each of these proteins includes a region called the bHLH domain, which determines the protein's 3-dimensional shape and enables it to target particular sequences of DNA. The bHLH family of transcription factors helps regulate the development of many organs and tissues before birth. During embryonic development, the TWIST1 protein is essential for the formation of cells that give rise to bone, muscle, and other tissues in the head and face. The TWIST1 protein also plays a role in the early development of the limbs. Researchers believe that the TWIST1 protein regulates several genes that are known to be key players in bone formation, including the FGFR2 and RUNX2 genes.

The following transcription factors affect gene expression:

• p53
• STAT3
• NF-1
• AREB6
• Sox9
• Msx-1

Tissue specificity:

Subset of mesodermal cells.

Molecular Function:

• Bhlh Transcription Factor Binding
• E-Box Binding
• Rna Polymerase Ii Transcription Factor Activity, Sequence-Specific Dna Binding
• Transcription Factor Binding

Biological Processes:

• Aortic Valve Morphogenesis
• Cardiac Neural Crest Cell Migration Involved In Outflow Tract Morphogenesis
• Cell Proliferation Involved In Heart Valve Development
• Cellular Response To Growth Factor Stimulus
• Cellular Response To Hypoxia
• Cranial Suture Morphogenesis
• Embryonic Camera-Type Eye Formation
• Embryonic Cranial Skeleton Morphogenesis
• Embryonic Digit Morphogenesis
• Embryonic Forelimb Morphogenesis
• Embryonic Hindlimb Morphogenesis
• Endocardial Cushion Morphogenesis
• Eyelid Development In Camera-Type Eye
• In Utero Embryonic Development
• Mitral Valve Morphogenesis
• Muscle Organ Development
• Negative Regulation Of Apoptotic Process
• Negative Regulation Of Cellular Senescence
• Negative Regulation Of Dna Damage Response, Signal Transduction By P53 Class Mediator
• Negative Regulation Of Double-Strand Break Repair
• Negative Regulation Of Histone Acetylation
• Negative Regulation Of Histone Phosphorylation
• Negative Regulation Of Osteoblast Differentiation
• Negative Regulation Of Oxidative Phosphorylation Uncoupler Activity
• Negative Regulation Of Peroxisome Proliferator Activated Receptor Signaling Pathway
• Negative Regulation Of Phosphatidylinositol 3-Kinase Signaling
• Negative Regulation Of Sequence-Specific Dna Binding Transcription Factor Activity
• Negative Regulation Of Skeletal Muscle Tissue Development
• Negative Regulation Of Transcription, Dna-Templated
• Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
• Negative Regulation Of Tumor Necrosis Factor Production
• Neural Tube Closure
• Neuron Migration
• Odontogenesis
• Ossification
• Osteoblast Differentiation
• Outer Ear Morphogenesis
• Palate Development
• Positive Regulation Of Angiogenesis
• Positive Regulation Of Cell Motility
• Positive Regulation Of Dna-Templated Transcription, Initiation
• Positive Regulation Of Endocardial Cushion To Mesenchymal Transition Involved In Heart Valve Formation
• Positive Regulation Of Epithelial Cell Proliferation
• Positive Regulation Of Epithelial To Mesenchymal Transition
• Positive Regulation Of Fatty Acid Beta-Oxidation
• Positive Regulation Of Gene Expression
• Positive Regulation Of Interleukin-6 Secretion
• Positive Regulation Of Monocyte Chemotactic Protein-1 Production
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Positive Regulation Of Transcription Regulatory Region Dna Binding
• Positive Regulation Of Tumor Necrosis Factor Production
• Regulation Of Bone Mineralization
• Rhythmic Process
• Transcription, Dna-Templated