A Gain-of-Function Mutation in KCNMA1 Causes Dystonia Spells Controlled With Stimulant Therapy

Guohui Zhang, Rebecca A. Gibson, Marie McDonald, Pengfei Liang, Po Wei Kang, Jingyi Shi, Huanghe Yang, Jianmin Cui, Mohamad A. Mikati

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish
Pages (from-to)1868-1873
Number of pages6
JournalMovement Disorders
Issue number10
StatePublished - Oct 1 2020


  • BK channelopathy
  • KCNMA1
  • dystonia
  • movement disorders
  • stimulants


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