A novel c.746T>G (p.Phe249Cys) missense mutation of KCNA1 segregated in the family members with episodic ataxia, myokymia, and malignant hyperthermia susceptibility.
Mutations in two neuronal ion-channel genes KCNA1 and CACNA1A abundantly expressed in the cerebellum account for the majority of the identified cases of episodic ataxia.
We conclude that mutations in the potassium channel gene (KCNA1) can cause severe neuromyotonia resulting in marked skeletal deformities even if episodic ataxia is not prominent.
In another group of dominant disorders, episodic ataxia type I and type 2 (EA-I, EA-2) and SCA6, the mutations affect genes that code for ion channels.
Recently, the association of one form of episodic ataxia (defined by the presence of additional myokymia) with point mutations in the potassium channel gene KCNA1 was described.
The syndrome in this family is linked to the recently discovered locus for inherited myokymia and paroxysmal ataxia on the human chromosome 12p, and a missense mutation is shown in the KCNA1 gene.