Cerebro-Costo-Mandibular syndrome (CCMS) is a rare congenital disorder comprising skeletal malformations in branchial arch derivatives and in the thoracic cage with striking rib gaps. Affected patients often have respiratory difficulties, associated with upper airway obstruction, reduced thoracic capacity and scoliosis (Tooley et al., 2016). The genetic cause of CCMS was recently identified as mutations in the gene called SNRPB, encoding Small Nuclear Ribonucleoprotein-associated Protein B and the isoform B’ (Lynch et al., 2014). SNRPB are components of the major spliceosome required for RNA splicing. The importance of accurate splicing is evident, as 15-50% of human genetic diseases arise from mutations involved in splicing. Recently, many craniofacial disorders have been found to be caused by genetic alterations in spliceosomal genes (Lehalle et al., 2015). Although, it is not known how mutations in such fundamental genes can cause specific phenotypes during embryogenesis.

Our group recently found that knock-down of SNRPB or other genes causing craniofacial disorders affects some signalling pathways that play crucial roles in the cartilage and bone formation in embryos. We currently investigate the molecular mechanism for tho in in vitro cultured cells.

Reference: Tooley, M. et al. (2016). Cerebro-Costo-Mandibular syndrome: Clinical, Radiological and Genetic Findings. American Journal of Medical Genetics 170:1115-26.