Metabolomics profiling of cleidocranial dysplasia
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Cleidocranial 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 methods
We 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.
We 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.
The 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.
This 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.
KeywordsCCD Metabolic changes RUNX2 Mutation Patients Protein structure
The work was supported by the Southern Medical University (grants PY2017N036); National Natural Science Foundation of China (grants 81571020 and 81771124); Natural Science Foundation of Guangdong Province (grants 2015A030313179).
Compliance with ethical standards
Conflict of interest
Z.Z. declares that he has no conflict of interest. K.L. declares that he has no conflict of interest. M.Y. declares that he has no conflict of interest. Q.L. declares that he has no conflict of interest. J.L. declares that he has no conflict of interest. P.Z. declares that he has no conflict of interest. Y.X. declares that he has no conflict of interest.
All procedures performed in our study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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