부산대학교 도서관

Background: The mutations of KCNMA1 BK‐type K+ channel have been identified in patients with various movement disorders. The underlying pathophysiology and corresponding therapeutics are lacking. Objectives: To report our clinical and biophysical characterizations of a novel de novo KCNMA1 variant, as well as an effective therapy for the patient's dystonia‐atonia spells. Methods: Combination of phenotypic characterization, therapy, and biophysical characterization of the patient and her mutation. Results: The patient had >100 dystonia‐atonia spells per day with mild cerebellar atrophy. She also had autism spectrum disorder, intellectual disability, and attention deficit hyperactivity disorder. Whole‐exome sequencing identified a heterozygous de novo BK N536H mutation. Our biophysical characterization demonstrates that N536H is a gain‐of‐function mutation with markedly enhanced voltage‐dependent activation. Remarkably, administration of dextroamphetamine completely suppressed the dystonia‐atonia spells. Conclusions: BK N536H is a gain‐of‐function that causes dystonia and other neurological symptoms. Our stimulant therapy opens a new avenue to mitigate KCNMA1‐linked movement disorders. © 2020 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]