PUBLICATION
Skeletal Class III Malocclusion Is Associated with ADAMTS2 Variants and Reduced Expression in a Familial Case
- Authors
- Yao, S., Zhou, X., Vona, B., Fan, L., Zhang, C., Li, D., Yuan, H., Du, Y., Ma, L., Pan, Y.
- ID
- ZDB-PUB-220924-22
- Date
- 2022
- Source
- International Journal of Molecular Sciences 23(18): (Journal)
- Registered Authors
- Keywords
- craniofacial abnormalities, developmental biology, genetic research, malocclusion, whole exome sequencing, zebrafish
- MeSH Terms
-
- HEK293 Cells
- ADAMTS Proteins/genetics
- Animals
- Mandible
- Malocclusion, Angle Class III*/pathology
- PubMed
- 36142585 Full text @ Int. J. Mol. Sci.
Abstract
Skeletal Class III malocclusion with maxillary deficiency is a severe maxillofacial disease with unclear pathogenic mechanisms. We recruited a Han Chinese family who was clinically diagnosed with skeletal Class III malocclusion and maxillary deficiency. Using whole exome sequencing, a missense variant in ADAMTS2 (NM_014244: c.3506G>T: p.G1169V) was identified and predicted as deleterious by in silico tools. We also found ADAMTS2 variants associated with deficient maxillary development in a cohort. ADAMTS2 expression in HEK293 cells showed significant decrease due to the variant, which was also consistent in dental pulp stem cells from the proband and a healthy control. In the adamts2-knockdown zebrafish model, the length and width of the ethmoid plate, as well as the length of the palatoquadrate became significantly shorter than the control group (p < 0.001), while there was no significant difference in the length and width of the mandible. The expression of Sox3, which was required in early embryonic craniofacial development, was significantly downregulated in the adamts2-knockdown zebrafish embryos. Bioinformatic and cellular studies showed that the decreased expression of ADAMTS2 may inhibit downstream ErbB signaling pathway transduction and restrain subsequent osteogenesis in human adult mesenchymal stromal cells. Collectively, these data showed that ADAMTS2 (c.3506G>T: p.G1169V) may confer susceptibility to risk of skeletal Class III malocclusion with maxillary deficiency.
Genes / Markers
Figure Gallery (4 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping