Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Spondylocostal dysostosis (SCD) is an inherited disorder with abnormal vertebral segmentation that results in extensive hemivertebrae, truncal shortening and abnormally aligned ribs. It arises during embryonic development by a disruption of formation of somites (the precursor tissue of the vertebrae, ribs and associated tendons and muscles). Four genes causing a subset of autosomal recessive forms of this disease have been identified: DLL3 (SCDO1: MIM 277300), MESP2 (SCDO2: MIM 608681), LFNG (SCDO3: MIM609813) and HES7 (SCDO4). These genes are all essential components of the Notch signalling pathway, which has multiple roles in development and disease. Previously, only a single SCD-causative missense mutation was described in HES7. In this study, we have identified two new missense mutations in the HES7 gene in a single family, with only individuals carrying both mutant alleles being affected by SCD. In vitro functional analysis revealed that one of the mutant HES7 proteins was unable to repress gene expression by DNA binding or protein heterodimerization.

Original publication




Journal article


Eur J Hum Genet

Publication Date





674 - 679


Amino Acid Sequence, Animals, Base Sequence, Basic Helix-Loop-Helix Transcription Factors, Cells, Cultured, Dysostoses, Family, Humans, Mice, Molecular Sequence Data, Mutation, Missense, Pedigree, Sequence Homology, Amino Acid, Spine, Transfection