You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
A de novo KCNA1 Mutation in a Patient with Tetany and Hypomagnesemia
Contributor:
van der Wijst, Jenny;
Konrad, Martin;
Verkaart, Sjoerd A.J.;
Tkaczyk, Marcin;
Latta, Femke;
Altmüller, Janine;
Thiele, Holger;
Beck, Bodo;
Schlingmann, Karl Peter;
de Baaij, Jeroen H.F.
Published:
S. Karger AG, 2018
Published in:
Nephron, 139 (2018) 4, Seite 359-366
Language:
English
DOI:
10.1159/000488954
ISSN:
1660-8151;
2235-3186
Origination:
Footnote:
Description:
Mutations in the <i>KCNA1</i> gene encoding the voltage-gated potassium (K<sup>+</sup>) channel Kv1.1 have been linked to rare neurological syndromes, episodic ataxia type 1 (EA1) and myokymia. In 2009, a <i>KCNA1</i> mutation was identified in a large family with autosomal dominant hypomagnesemia. Despite efforts in establishing a genotype-phenotype correlation for the wide variety of symptoms in EA1, little is known on the serum magnesium (Mg<sup>2+</sup>) levels in these patients. In the present study, we describe a new de novo <i>KCNA1</i> mutation in a Polish patient with tetany and hypomagnesemia. Electrophysiological and biochemical analyses were performed to determine the pathogenicity of the mutation. A female patient presented with low serum Mg<sup>2+</sup> levels, renal Mg<sup>2+</sup> wasting, muscle cramps, and tetanic episodes. Whole exome sequencing identified a p.Leu328Val mutation in <i>KCNA1</i> encoding the Kv1.1 K<sup>+</sup> channel. Electrophysiological examinations demonstrated that the p.Leu328Val mutation caused a dominant-negative loss of function of the encoded Kv1.1 channel. Cell surface biotinylation showed normal plasma membrane expression. Taken together, this is the second report linking <i>KCNA1</i> with hypomagnesemia, thereby emphasizing the need for further evaluation of the clinical phenotypes observed in patients carrying <i>KCNA1</i> mutations.