A Missense Mutation in DUSP6 is Associated with Class III Malocclusion

Class III malocclusion is a common dentofacial phenotype with a variable prevalence according to ethnic background. The etiology of Class III malocclusion has been attributed mainly to interactions between susceptibility genes and environmental factors during the morphogenesis of the mandible and ma...

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Bibliographic Details
Published in:Journal of dental research 2013-10, Vol.92 (10), p.893-898
Main Authors: Nikopensius, T., Saag, M., Jagomägi, T., Annilo, T., Kals, M., Kivistik, P.A., Milani, L., Metspalu, A.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Age
Aged
Chromosome 12
Chromosomes
Chromosomes, Human, Pair 12 - genetics
Craniofacial growth
Dental occlusion
Dentistry
Developmental stages
DNA Mutational Analysis
Dual Specificity Phosphatase 6 - genetics
Environmental factors
Estonia
Etiology
Female
Fibroblast growth factor receptors
Genes
Genes, Dominant
Genetic Linkage
Genomes
Genomics
Genotype & phenotype
Heredity
Humans
Influence
Male
Malocclusion, Angle Class III - genetics
Mandible
MAP kinase
Maxilla
Middle Aged
Missense mutation
Morphogenesis
Mutation
Mutation, Missense
Orthodontics
Patients
Pedigree
Phenotype
Phenotypes
Phenylalanine - genetics
Serine - genetics
Studies
Transcription activation
Values
Young Adult
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Description
Summary:Class III malocclusion is a common dentofacial phenotype with a variable prevalence according to ethnic background. The etiology of Class III malocclusion has been attributed mainly to interactions between susceptibility genes and environmental factors during the morphogenesis of the mandible and maxilla. Class III malocclusion shows familial recurrence, and family-based studies support a predominance of an autosomal-dominant mode of inheritance. We performed whole-exome sequencing on five siblings from an Estonian family affected by Class III malocclusion. We identified a rare heterozygous missense mutation, c.545C>T (p.Ser182Phe), in the DUSP6 gene, a likely causal variant. This variant co-segregated with the disease following an autosomal-dominant mode of inheritance with incomplete penetrance. Transcriptional activation of DUSP6 has been presumed to be regulated by FGF/FGFR and MAPK/ERK signaling during fundamental processes at early stages of skeletal development. Several candidate genes within a linkage region on chromosome 12q22-q23 – harboring DUSP6 – are implicated in the regulation of maxillary or mandibular growth. The current study reinforces that the 12q22-q23 region is biologically relevant to craniofacial development and may be genetically linked to the Class III malocclusion.
ISSN:0022-0345
1544-0591
DOI:10.1177/0022034513502790