Ablepharon and craniosynostosis in a patient with a localized TWIST1 basic domain substitution

The TWIST family is a group of highly conserved basic helix –loop–helix transcription factors. In humans,TWIST1 haploinsufficiency causes Saethre –Chotzen syndrome, which is characterized by craniosynostosis. Heterozygous localizedTWIST1 andTWIST2 basic domain substitutions exert antimorphic effects to cause Sweeney –Cox syndrome, Barber–Say syndrome, and ablepharon‐macrostomia syndrome, respectively. Sweeney–Cox syndrome, Barber–Say syndrome, and ablepharon‐macrostomia syndrome share the facial features of ablepharon, hypertelorism, underdevelopment of the eyelids, and cheek pads adjacent to the co rners of the mouth. Existence of phenotypic overlap between Saethre–Chotzen syndrome and Sweeney–Cox syndrome remains unknown. Herein, we document a male infant with the distinctive facial features of ablepharon, hypertelorism, cheek pads adjacent to the corners of the mouth, and bilateral coron al suture craniosynostosis who had a de novo heterozygous mutation in the basic domain ofTWIST1, that is, c.351C>G p.Glu117Asp. The pathogenicity of this variant was supported by in silico and in vivo evidence. Our review showed that Sweeney –Cox syndrome appears to share many characteristics with Barber–Say syndrome and ablepharon‐macrostomia syndrome except for craniosynostosis, which is a cardinal feature of Saethre–Chotzen syndrome. An amino acid substitution from Glu117 to Asp, both of which are the sole members of negative ly charged amino acids, resu...

Source: American Journal of Medical Genetics Part A - November 18, 2018 Category: Genetics & Stem Cells Authors: Toshiki Takenouchi, Yoshiaki Sakamoto, Hironori Sato, Hisato Suzuki, Tomoko Uehara, Yoshiteru Ohsone, Kenjiro Kosaki Tags: CLINICAL REPORT Source Type: research