Metabolomics profiling of cleidocranial dysplasia

• Published in: Clinical oral investigations Vol. 23; no. 3; pp. 1031 - 1040
• Main Authors: Zhang, Zhaoqiang, Li, Kefeng, Yan, Mengdie, Lin, Qiuping, Lv, Jiahong, Zhu, Ping, Xu, Yue
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-03-2019; Springer Nature B.V
• Subjects: Bone dysplasia; Cbfa-1 protein; Craniofacial syndromes; Dentistry; Medicine; Metabolic pathways; Metabolism; Metabolites; Metabolomics; Mutation; Original Article; Protein structure; Proteins; Skeleton; Mutation; Metabolic changes; CCD; Patients; Protein structure; RUNX2
• ISSN: 1432-6981; 1436-3771
• DOI: 10.1007/s00784-018-2496-9

Objectives
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.
Results
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.
Conclusions
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.
Clinical relevance
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.