New Gene Discovered for Rare Genetic Disorder – Cerebro-costo-mandibular Syndrome

Lynch, Danielle et al.  Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro–costo–mandibular syndrome.  Nature Communications 5:4483.

From Genes to Proteins

Genes contain the code for proteins that are required for our body to function.  Before this genetic code is translated into a protein, an intermediate product is created known as mRNA.  Genes consist of coding sequences that becomes part of the protein (exons) as well as portions that are cut or spliced out when the mRNA is formed (introns).  This splicing process, is in part performed by a group of proteins referred to as the spliceosome and allows for a number of different proteins to be produced from one single gene (referred to as alternative splicing).

Figure 1a, b.  A diagram of alternative splicing where one gene leads to the production of 2 different mRNAs.  spl=spliceosome.  Several regulatory factors determine which exons are recognized by the spliceosome.



Cerebro-costo-mandibular syndrome is a rare genetic disorder characterized by any combination of an abnormally small jaw, cleft palate, rib abnormalities and intellectual disability of varying severity.  Occasionally the jaw and palate abnormalities lead to breathing difficulties in infancy.  Prior to the study completed by Lynch and colleagues, there was no known gene associated with the disorder. 

This research discovered mutations in a gene responsible for coding a protein that is part of the spliceosome complex, SNRPB.    These mutation leads to an overall imbalance in the relative amount of the two protein products that are derived from the alternative splicing of the SNRPB  gene.  This in turn, affects the regulatory properties spliceosome itself and consequently,  its downstream targets.

Ten families from various countries participated in the research which led to the gene discovery and provided further evidence of the RNA splicing mechanism by which fetal development is regulated.   Danielle Lynch, a doctoral candidate at the University of Calgary and the principal researcher for the project, presented the findings at the European Society of Human Genetics Meeting, held in Milan, Italy in June of this year and the article was subsequently published in the prestigious science journal Nature Communications in July, 2014.