Deletion of ERF and CIC causes abnormal skull morphology and global developmental delay

The ETS2 repressor factor (ERF) is a transcription factor in the RAS-MEK-ERK signal transduction cascade that regulates cell proliferation and differentiation, and pathogenic sequence variants in the ERF gene cause variable craniosynostosis inherited in an autosomal dominant pattern. The reported ERF variants are largely loss-of-function, implying haploinsufficiency as a primary disease mechanism; however, ERF gene deletions have not been reported previously. Here we describe three probands with macrocephaly, craniofacial dysmorphology, and global developmental delay.

Citation:
Singh R, Cohen ASA, Poulton C, Hjortshøj TD, ...... Baynam G, et al. Deletion of ERF and CIC causes abnormal skull morphology and global developmental delay. Cold Spring Harb Mol Case Stud. 2021;7(3).

Keywords:
Congenital strabismus; craniosynostosis; global developmental delay; intellectual disability; macrocephaly at birth; widely patent coronal suture

Abstract:
The ETS2 repressor factor (ERF) is a transcription factor in the RAS-MEK-ERK signal transduction cascade that regulates cell proliferation and differentiation, and pathogenic sequence variants in the ERF gene cause variable craniosynostosis inherited in an autosomal dominant pattern. The reported ERF variants are largely loss-of-function, implying haploinsufficiency as a primary disease mechanism; however, ERF gene deletions have not been reported previously. Here we describe three probands with macrocephaly, craniofacial dysmorphology, and global developmental delay.