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

Abstract

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.

Craniofacial Morphology of Class III Malocclusion with DUSP6 Gene: Mutation and Non-Mutation Groups

“…Furthermore, a deficient or extreme vertical facial height also commonly demonstrated and influence on the therapeutic and diagnostic verdicts. Since long it has been said that class III malocclusion is predisposed by genetics 16,17) and several environmental factors like growth 18) , Endocrine imbalances 19) , hormonal disturbance 20) , congenital anatomic defects 21) etc. Apparently, a characteristic, genetically inherited mandibular morphology is recognized timely on in ontogeny and perceptible in early childhood 22) .…”

“…Nevertheless, it is commonly said about the genetic influence on class III malocclusion, very few works has been done to assess the quantitative character of heredity in the development of this condition. Different studies discussed various susceptible loci, genes and genetic association for the class III malocclusion 9,16,23) . However, no study has been found to evaluate the craniofacial characteristics of genetically exaggerated class III malocclusion.…”

Genetic Factors Affecting Facial Growth

“…(Ishii et al, 2002) Considering this heterogeneity, and possible epistasis (the interaction between or among gene products on their expression) and even epigenetics, it is not surprising that genetic linkage and candidate gene studies to date have indicated the possible location of genetic loci influencing this trait in several chromosomal locations (see figure 5). (Falcão-Alencar et al, 2010;Frazier-Bowers et al, 2009;Jang et al, 2010;Li et al, 2010;Li et al, 2011;Tassopoulou-Fishell et al, 2011;Xue et al, 2010;Yamaguchi et al, 2005) Fig. 5.…”

Class III malocclusion: an argument for early orthodontic treatment

“…For example, analyses of Korean and Japanese families showed mandibular prognathism is associated with chromosome regions 1p36, 6q25, and 19q13.2 [5]. Colombian families have shown Class III malocclusion is as--sociated with regions 1p22.1, 3q26.2, 11q22, 12q13.13, and 12q23 [6]. Analyses of Han Chi--nese people showed regions 14q24.3--q31.2 influence mandible growth [7].…”