RESUMO
Epilepsy affects approximately 1% of the world's population. Genetic factors and acquired etiologies, as well as a range of environmental triggers, together contribute to epileptogenesis. We have identified a family with three daughters affected with progressive myoclonus epilepsy with ataxia. Clinical details of the onset and progression of the neurologic presentation, epileptic seizures, and the natural history of progression over a 10-year period are described. Using autozygosity genetic mapping, we identified a high likelihood homozygous region on chromosome 7p12.1-7q11.22. We subsequently applied whole-exome sequencing and employed a rare variant prioritization analysis within the homozygous region. We identified p.Tyr276Cys in the potassium channel tetramerization domain-containing seven gene, KCTD7, which is expressed predominantly in the brain. Mutations in this gene have been implicated previously in epileptic phenotypes due to disturbances in potassium channel conductance. Pathogenicity of the mutation was supported by bioinformatic predictive analyses and variant cosegregation within the family. Further biologic validation is necessary to fully characterize the pathogenic mechanisms that explain the phenotypic causes of epilepsy with ataxia in these patients.
Assuntos
Ataxia/genética , Mutação/genética , Epilepsias Mioclônicas Progressivas/genética , Canais de Potássio/genética , Adolescente , Ataxia/complicações , Pré-Escolar , Mapeamento Cromossômico , Cromossomos Humanos Par 7/genética , Cisteína/genética , Eletroencefalografia , Exoma/genética , Feminino , Ligação Genética , Humanos , Lactente , Masculino , Epilepsias Mioclônicas Progressivas/complicações , Tirosina/genéticaRESUMO
Using a nationally representative sample of participants, this study investigates childhood victimization in the home and adolescent violent victimization in the community on the risk of being a victim of intimate partner violence (IPV), general violence, or both during early adulthood. The study findings indicate being left home alone and being physically abused during childhood, and adolescent violent victimization in the community had strong independent effects on an individual's likelihood of becoming a victim of IPV, general violence, or both in early adulthood. The study findings suggest a consistent pattern of victimization across the life course, and intervention programs need to be developed that address the specific needs of children and adolescents at high risk for home and community violent victimization.