Because the effectiveness of HF-SCS may be adversely affected by deterioration of these fibers and/or the condition of the animal, low-frequency (50 Hz) SCS (LF-SCS) was also performed and served as a control.
Variants were identified most frequently in TCF12 (N = 22) and EFNB1 (N = 8), typically in individuals with nonsyndromic coronal craniosynostosis or TWIST1-negative clinically suspected Saethre-Chotzen syndrome.
This distance is more significantly altered in FGFR-related brachycephaly syndromes (especially Crouzon and Pfeiffer syndromes), than Saethre-Chotzen syndrome (TWIST1 mutation) and isolated non-syndromic bicoronal synostosis.
Saethre-Chotzen syndrome is an autosomal dominantly inherited disorder caused by mutations in the twist family basic helix-loop-helix transcription factor 1 (TWIST1) gene.
This is the first demonstration that non-coding SNVs of TWIST1 can cause SCS, and highlights the importance of screening the 5' UTR in clinically diagnosed SCS patients without a coding mutation.
Knock-down of C-ROS-1 expression in TWIST-1 haploinsufficient calvarial cells derived from SCS patients was associated with decreased capacity for osteogenic differentiation in vitro.
Although about one hundred different TWIST1 mutations have been reported in patients with the dominant haploinsufficiency Saethre-Chotzen syndrome (typically associated with craniosynostosis), substitutions uniquely affecting the Glu117 codon were not observed previously.
Our study demonstrates that MD simulations provide a structural explanation for the loss-of-function associated with the SCSTWIST1 mutation and provides a proof of concept of the predictive value of these MD simulations.
In humans, Twist1 malfunction was first linked to Saethre-Chotzen syndrome and later identified to play an essential role in tumor initiation, stemness, angiogenesis, invasion, metastasis, and chemo-resistance in a variety of carcinomas, sarcomas, and hematological malignances.
In addition to 10 different, known mutations in FGFR1,FGFR2 or FGFR3, one novel missense mutation, c.528C>G(p.Ser176Arg), was detected in the TWIST1 gene of a patient with Saethre-Chotzen syndrome.
This review first summarizes the roles of Twist1 in embryo development and Saethre-Chotzen syndrome followed by a discussion of Twist1's critical functions in cancer.
We highlight the determinant role of the interhelical loops in maintaining the TWIST1-DNA complex structures and provide a structural explanation for the loss of function associated with several TWIST1 mutations/insertions observed in Saethre-Chotzen syndrome patients.
A specific genetic etiology can be identified in ∼21% of cases, including mutations of TWIST1, which encodes a class II basic helix-loop-helix (bHLH) transcription factor, and causes Saethre-Chotzen syndrome, typically associated with coronal synostosis.
Saethre-Chotzen syndrome (acrocephalosyndactyly type III; SCS; OMIM #101400) is an autosomal dominant craniosynostosis syndrome characterized by craniofacial and mild limb abnormalities.
A specific genetic etiology can be identified in ∼21% of cases, including mutations of TWIST1, which encodes a class II basic helix-loop-helix (bHLH) transcription factor, and causes Saethre-Chotzen syndrome, typically associated with coronal synostosis.
This case illustrates the important contribution of array CGH to the identification of TWIST microdeletions, even in a patient not showing the phenotype typical of Saethre–Chotzen syndrome.