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In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
A missense mutation in DUSP6 is associated with Class III malocclusion.
T Nikopensius1, M Saag, T Jagomägi
1Institute of Molecular and Cell Biology, University of Tartu, Estonia.
Journal of Dental Research
|August 23, 2013
Summary
A rare mutation in the DUSP6 gene was identified in an Estonian family with Class III malocclusion, suggesting a genetic link to craniofacial development and skeletal growth disorders.
Area of Science:
- Genetics
- Orthodontics
- Developmental Biology
Background:
- Class III malocclusion is a common craniofacial developmental disorder with a significant genetic component.
- Previous studies suggest autosomal-dominant inheritance and implicate gene-environment interactions in its etiology.
- The 12q22-q23 chromosomal region is a potential locus for genes regulating craniofacial growth.
Purpose of the Study:
- To identify genetic variants associated with Class III malocclusion in an affected family.
- To investigate the role of the DUSP6 gene in craniofacial development.
- To confirm the inheritance pattern and penetrance of the identified mutation.
Main Methods:
- Whole-exome sequencing was performed on five siblings from an Estonian family with Class III malocclusion.
- Segregation analysis was conducted to confirm the co-inheritance of the identified variant.
- Literature review on DUSP6 function and its role in FGF/FGFR and MAPK/ERK signaling pathways.
Main Results:
- A rare heterozygous missense mutation (c.545C>T, p.Ser182Phe) in the DUSP6 gene was identified.
- This DUSP6 variant co-segregated with Class III malocclusion in the family, exhibiting autosomal-dominant inheritance with incomplete penetrance.
- The DUSP6 gene, regulated by FGF/FGFR and MAPK/ERK signaling, is located in the 12q22-q23 region previously linked to craniofacial development.
Conclusions:
- The identified DUSP6 mutation is a likely causal variant for Class III malocclusion in this family.
- This finding reinforces the 12q22-q23 region's importance in craniofacial development and its genetic linkage to Class III malocclusion.
- DUSP6 plays a critical role in skeletal development, potentially through FGF/FGFR and MAPK/ERK signaling pathways.
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