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.