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Evidence of Linkage in a Hispanic Cohort with a Class III Dentofacial Phenotype

¹ Department of Orthodontics, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7450, USA;
² Faculty of Dentistry, University of Antioquia, Medellin, Colombia;
³ Private Practice Orthodontics, Raleigh, NC, 27609, USA; and
⁴ University of North Carolina at Chapel Hill, Department of Genetics, Chapel Hill, NC 27599, USA

Correspondence: ^* corresponding author, sylvia_frazier{at}dentistry.unc.edu

Despite the prevalence of craniofacial disorders, the genetic contribution remains poorly understood. Class III malocclusion represents a specific craniofacial problem that can be handicapping, both functionally and socially. We hypothesized that the Class III phenotype is genetically linked to specific loci that regulate maxillary or mandibular growth. To determine the region linked to the Class III phenotype in four Hispanic families, we performed a genome-wide scan and linkage analysis using 500 microsatellite markers. Pedigree and linkage analyses revealed that the Class III phenotype (primarily maxillary deficiency) segregates in an autosomal-dominant manner, and that 5 loci (1p22.1, 3q26.2, 11q22, 12q13.13, and 12q23) are suggestive of linkage. Candidate genes within the 12q23 region (ZLR=2.93) include IGF1, HOXC, and COL2A1. Chromosome 1 results (ZLR=2.92) were similar to those reported previously in an Asian cohort with mandibular prognathism, suggesting that a common upstream genetic element may be responsible for both mandibular prognathism and maxillary deficiency.

Key Words: Class III phenotype • malocclusion • dentofacial deformity • Hispanic

Journal of Dental Research, Vol. 88, No. 1, 56-60 (2009)
DOI: 10.1177/0022034508327817


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