LAUSR

ObjectivesCleidocranial dysplasia (CCD) is a rare autosomal-dominantly inherited skeletal dysplasia that is predominantly associated with heterozygous mutations of RUNX2. However, no information is available regarding metabolic changes associated with CCD at present.Materials and methodsWe analyzed members of a CCD family and checked for mutations in the RUNX2 coding sequence using the nucleotide BLAST program. The 3D protein structure of mutant RUNX2 was predicted by I-TASSER. Finally, we analyzed metabolites extracted from plasma using LC-MS/MS.ResultsWe identified a novel mutation (c.1061insT) that generates a premature termination in the RUNX2 coding region, which, based on protein structure prediction models, likely alters the protein’s function. Interestingly, metabolomics profiling indicated that 30 metabolites belonging to 13 metabolic pathways were significantly changed in the CCD patients compared to normal controls.ConclusionsThe results highlight interesting correlations between a RUNX2 mutation, metabolic changes, and the clinical features in a family with CCD. The results also contribute to our understanding of the pathogenetic processes underlying this rare disorder.Clinical relevanceThis study provides the first metabolomics profiling in CCD patients, expands our insights into the pathogenesis of the disorder, may help in diagnostics and its refinements, and may lead to novel therapeutic approaches to CCD.