IDENTIFICATION OF GENETIC VARIANTS THROUGH WHOLE EXOMESEQUENCING IN PHENOTYPES WITH SKELETAL CLASS IIMALOCCLUSION BAD RESPONDERS

Skeletal malocclusions are complex craniofacial growth and developmental problems due to hereditary and environmental factors. They are a set of human morphologic characteristics that both exceed or present deficiency of maxillary and mandibular dimensions, resulting in an improper relationship of the jaws that distorts the balance of the face. Class II malocclusion is one of the most frequent orthodontic issues as it occurs in about one-third of the Western European population. It can result from an anterior displacement of the maxilla, a backside position of the mandible, or any combination of these aspects. Although the efficacy of Class II malocclusion treatments is still debated in the literature, orthopedic functional appliances used at the pubertal growth peak seem to be the best option for the improvement of this skeletal alteration. The nature of the variations that induces improvements of Class II malocclusion is not completely clear yet: some authors suggest that the effects of functional therapy are limited to the dentoalveolar structures of the jaws; others assert that this kind of device influence the mandibular growth thus resulting in a modification of the jaw relationship. Few studies have already investigated the correlation between craniofacial growth patterns and genetic markers. The evolution of molecular genetics could help in differentiating the etiologies of the skeletal alterations. Single-nucleotide polymorphisms (SNPs) are the most frequent variations in the human genome and are associated with different skeletal malocclusion phenotypes. Genes encoding proteins involved in bone or cartilage biology are involved in facial development biotypes. Although it is difficult to define the genetic pattern of the craniofacial malocclusions because of their polygenic nature, data from the human genome have been used to map inherited conditions related to dentofacial development. These advancements in molecular genetics may lead to a genetic diagnosis of dentofacial malocclusions for the clinicians. However, more genetic studies are required to discover all genes associated with skeletal growth variations. Previous genetic studies about the association between gene variants and skeletal malocclusion have only investigated the association between SNPs and craniofacial phenotypes. The technology to acquire comprehensive genetic data provides researchers to better understand the susceptibility to skeletal malocclusion and the different responsiveness of patients to the same orthopedic treatment. The aim of the present research will be therefore to identify a genetic mutation responsible for the development of severe Class II cases that do not respond to the first line treatment improving the predictive accuracy of classical clinical risk factors.