XB-ART-34974Neurogenetics. April 1, 2007; 8 (2): 131-5.
Functional analysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia.
Myokymia is characterized by spontaneous, involuntary muscle fiber group contraction visible as vermiform movement of the overlying skin. Myokymia with episodic ataxia is a rare, autosomal dominant trait caused by mutations in KCNA1, encoding a voltage-gated potassium channel. In the present study, we report a family with four members affected with myokymia. Additional clinical features included motor delay initially diagnosed as cerebral palsy, worsening with febrile illness, persistent extensor plantar reflex, and absence of epilepsy or episodic ataxia. Mutation analysis revealed a novel c.676C>A substitution in the potassium channel gene KCNA1, resulting in a T226K nonconservative missense mutation in the Kv1.1 subunit in all affected individuals. Electrophysiological studies of the mutant channel expressed in Xenopus oocytes indicated a loss of function. Co-expression of WT and mutant cRNAs significantly reduced whole-oocyte current compared to expression of WT Kv1.1 alone.
PubMed ID: 17136396
PMC ID: PMC1820748
Article link: Neurogenetics.
Grant support: DC01919 NIDCD NIH HHS , R01 DC001919 NIDCD NIH HHS , DC01919 NIDCD NIH HHS
Genes referenced: kcna1
Article Images: [+] show captions
|Fig. 1. Family pedigree. Squares indicate males, circles indicate females. Blackened symbols denote individuals with myokymia. Alleles at codon 226 are indicated (Thr = wild-type, Lys = mutation)|
|Fig. 2. Sequence chromatograms demonstrating c.676C>A resulting in T226K substitution in KCNA1. A DNA sequence from an affected patient (I-2) heterozygous for the mutation (top) and from a normal control (bottom) are presented|