Subject(s)
Carrier Proteins/genetics , Facial Injuries/genetics , Mutation , Nerve Tissue Proteins/genetics , Self-Injurious Behavior/genetics , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Phenotype , SyndromeABSTRACT
Traumatic dental injuries are a major cause of morbidity among children. Investigation of risk factors of dental trauma is important to take preventive measures in patients at high risk for tooth accidents. The aim of this work was to conduct a pilot study in twins, assessing concordance of suffered traumatic dental and facial injuries. Comparison of concordances between monozygotic and dizygotic twin pairs was performed in order to investigate possible genetically determined accident-proneness. Standardized interviews were conducted focusing on the frequency of orofacial accidents and their circumstances. In addition, the front teeth of all participating twins were clinically examined. A total of 104 twins (52 twin pairs) were surveyed: 31 of the 52 twin pairs were DZ and 21 pairs were MZ. 36 (34.6%) of the 104 interviewees had already suffered from a tooth injury, whereas 53 (51%) of the participants had experienced a facial injury. Investigation of concordances of suffered traumatic dental injuries revealed that 66.7% of the MZ twin pairs and 58.1% of the DZ pairs were concordant. With respect to facial traumata, 52.4% of the MZ pairs compared to 58.1% of the DZ pairs were concordant. Differences between zygosity were not statistically significant (P >/= 0.05). With the present pilot study, no statistical evidence of genetic risk for dental and facial injuries could be displayed. On the contrary, environmental factors seem to dominate in determining an individual's risk for orofacial traumata.
Subject(s)
Tooth Injuries/genetics , Twins/genetics , Accident Proneness , Adolescent , Adult , Cuspid/injuries , Dental Enamel/injuries , Facial Injuries/genetics , Female , Genetic Predisposition to Disease/genetics , Humans , Incisor/injuries , Lacerations/genetics , Lip/injuries , Male , Pilot Projects , Risk Factors , Tooth Avulsion/genetics , Tooth Crown/injuries , Tooth Fractures/genetics , Tooth, Deciduous/injuries , Twins, Dizygotic/genetics , Twins, Monozygotic/genetics , Young AdultABSTRACT
Obsessive-compulsive disorder (OCD) is an anxiety-spectrum disorder characterized by persistent intrusive thoughts (obsessions) and repetitive actions (compulsions). Dysfunction of cortico-striato-thalamo-cortical circuitry is implicated in OCD, although the underlying pathogenic mechanisms are unknown. SAP90/PSD95-associated protein 3 (SAPAP3; also known as DLGAP3) is a postsynaptic scaffolding protein at excitatory synapses that is highly expressed in the striatum. Here we show that mice with genetic deletion of Sapap3 exhibit increased anxiety and compulsive grooming behaviour leading to facial hair loss and skin lesions; both behaviours are alleviated by a selective serotonin reuptake inhibitor. Electrophysiological, structural and biochemical studies of Sapap3-mutant mice reveal defects in cortico-striatal synapses. Furthermore, lentiviral-mediated selective expression of Sapap3 in the striatum rescues the synaptic and behavioural defects of Sapap3-mutant mice. These findings demonstrate a critical role for SAPAP3 at cortico-striatal synapses and emphasize the importance of cortico-striatal circuitry in OCD-like behaviours.
