Recessive Symptomatic Focal Epilepsy and Mutant Contactin-Associated Protein-like 2

作者：Kevin A. Strauss, Erik G. Puffenberger, Matthew J. Huentelman, Steven M. Gottlieb, Seth E Dobrin, Jennifer M. Parod, Dietrich A. Stephan, D. Holmes Morton · 发表于：New England Journal of Medicine · 年份：2006 · DOI：10.1056/nejmoa052773 · 被引用次数：641 · 研究领域：Ion channel regulation and function、Genetic Neurodegenerative Diseases、Mitochondrial Function and Pathology

Contactin-associated protein-like 2 (CASPR2) is encoded by CNTNAP2 and clusters voltage-gated potassium channels (K(v)1.1) at the nodes of Ranvier. We report a homozygous mutation of CNTNAP2 in Old Order Amish children with cortical dysplasia, focal epilepsy, relative macrocephaly, and diminished deep-tendon reflexes. Intractable focal seizures began in early childhood, after which language regression, hyperactivity, impulsive and aggressive behavior, and mental retardation developed in all children. Resective surgery did not prevent the recurrence of seizures. Temporal-lobe specimens showed evidence of abnormalities of neuronal migration and structure, widespread astrogliosis, and reduced expression of CASPR2.