Deletion of the TWIST gene in a large five‐generation family

Abstract

In this article, we describe a large five-generation family with characteristics of the Saethre-Chotzen syndrome as well as of the blepharophimosis ptosis epicanthus inversus syndrome. Segregating with their phenotype is a deletion of the chromosome 7p21 TWIST gene locus. The TWIST gene indeed is involved in Saethre-Chotzen syndrome, a craniosynostosis syndrome further characterized by specific facial and limb abnormalities. However, only two members of our family exhibited craniosynostosis. This report demonstrates that the genetics of craniofacial anomalies are less straightforward than they sometimes appear to be. Not only craniosynostosis, but also subtle facial deformities could be indicative of an abnormality of the TWIST gene. In conclusion, the clinical spectrum of genetic abnormalities of the TWIST gene is highly variable. We therefore recommend that genetic analysis of the TWIST gene locus, including fluorescence in situ hybridization, should be considered in familial cases of facial and eyelid abnormalities without the presence of craniosynostosis.

Saethre-Chotzen syndrome: Case report and literature review

“…Dollfus et al 35 Nascimento et al 38 Heer et al 33 De Heer et al 39 Chun et al 34 Foo et al 24 Number…”

Nonsyndromic brachydactyly type D and type E mapped to 7p15 in healthy children and adults from the jirel ethnic group in eastern nepal

“…Mutations of TWIST are implicated in a number of skeletal dysplasias and syndromes including dysplastic skeletal elements. These include pediatric osteosarcomas (Entz‐Werle et al, ) and Saethre‐Chotzen syndrome (De Heer et al ; el Ghouzzi et al ; Krebs et al ) which includes syndactyly as part of its phenotype. Additionally, a contiguous gene syndrome on 7p resulting in a digit anomaly involves a deletion of TWIST and a deletion of the HOXA cluster (Kosaki et al, ).…”

Expression of twist gene in primary liver cancer

“…It belongs to the basic-helix-loop-helix (bHLH) family of transcription factors and is quite similar in the bHLH carboxy-terminal domains [7][8][9] . In mammals, Twist contributes to morphogenesis of the cranial neural tube and limb development [10][11][12] .…”

“…The Twist gene maps to 7p21 and mutations in the gene have been reported in the Saethre-Chotzen form of craniosynostosis [13] . Although the function of Twist is not fully clear at the molecular level, Twist has been indicated as a potential oncogene interfering with p53-related pathways leading to preventing myc-induced apoptosis in mouse embryonal fibroblasts [14][15][16] . Twist is also found to be involved in the suppression of differentiation and protection of apoptosis through inhibition of p21Waf1 via both p53-dependent and -independent pathways [17,18] .…”