Phenotype–genotype correlations of facial width and height proportions in patients with Class II malocclusion

Abstract

Objectives To characterize soft tissue facial height and width variation in Class II malocclusion and test for correlations with genes HMGA2, AJUBA and ADK. Setting and Sample Population Nine facial proportions were estimated from 2D frontal repose photographs of 330 Caucasian adults with Class II malocclusion. Material & Methods After adjustments for age and gender, the facial proportions were submitted to a principal component analyses (PCA). The most meaningful phenotypic variations were correlated with SNPS rs7924176 (ADK), rs17101923 (HMGA2), and rs997154 (AJUBA) genotyped in 106 individuals. Results PCA resulted in 4 principal components (PCs) which explained 75% of total variation. PC1 captured variation in the intercanthus distance and explained 28% of total variation. PC2 explained 21% of the variations in facial taper and facial index. PC3 explained 14% and reflected variations in the vertical dimension of the lower face. PC4 explained 12% and captured variations in distance between the eyes, width of the commissures, and the length of the superior aspect of the lower face height, corresponding to the vertical dimension of the philtrum of the upper lip. A suggestive association (p<0.05) was observed between PC4 and rs997154 corroborating the role of AJUBA in variation of facial dimensions. Conclusion 2D frontal photographs can be used to derive quantitative measures of soft tissue phenotypes that are of clinical relevance. The methods described are suitable for discovery and replication of associations between genotypes and malocclusion phenotypes.

Linear and Volumetric Mandibular Asymmetries in Adult Patients With Different Skeletal Classes and Vertical Patterns: A Cone-Beam Computed Tomography Study

“…Since Ricketts uses Gnation point, the authors considered this angle to be more reliable. Other studies on craniofacial structures classify the patients and make associations based on phenotypic clusters thus allowing clinical interpretation 39 , 40 . However, studies on mandibular shape and asymmetries classify patients according to vertical pattern and skeletal class like in our study, which allow more reliable comparisons between studies 1 , 28 , 32 , 38 …”

HMGA Genes and Proteins in Development and Evolution

“…By genotyping the different individuals, two independent studies identified alternative haplotypes, respectively favoring large or small beak dimensions; SNPs were found in the HMGA2 genomic region and this gene was indicated as the prime candidate to mediate this phenotypic variation because of its described effects on organ and body size; this phenotypic variation may potentially lead to ecological segregation and eventually to speciation [279,[281][282][283]. Beak development is strictly connected to NCCs [141] and therefore direct support for an involvement of HMGA2 in craniofacial development and evolution comes from the aforementioned work on Xenopus [39], and from the observations of craniofacial disturbances in the rabbit dwarf mutant [87] and in the hmga2 −/− pygmy mouse [53]; indirect support comes from studies that suggest the HMGA2 gene to be associated to craniofacial size and shape [284][285][286][287][288].…”

Candidate gene analyses of 3-dimensional dentoalveolar phenotypes in subjects with malocclusion

“…TBX1 is a major candidate gene causal for 22q11 deletion syndrome associated with congenital heart defects resulting from incorrect left-to-right patterning important for asymmetric cardiac morphogenesis 42 as well as craniofacial and dental anomalies including cleft palate. 43 The LIM protein AJUBA has previously shown an association with soft tissue facial width phenotypes, 44,45 and it is also required for expression of early developmental genes that determine left-right body axis patterning. 46 As discussed above, SNAI3 was largely associated with skeletal phenotypes in malocclusion patients in our previous study.…”