A de novo KCNA1 Mutation in a Patient with Tetany and Hypomagnesemia

Medientyp: E-Artikel

Titel: A de novo KCNA1 Mutation in a Patient with Tetany and Hypomagnesemia

Beteiligte: 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.

Erschienen: S. Karger AG, 2018

Sprache: Englisch

DOI: 10.1159/000488954

ISSN: 1660-8151; 2235-3186

Entstehung:

Anmerkungen:

Beschreibung: Mutations in the KCNA1 gene encoding the voltage-gated potassium (K+) channel Kv1.1 have been linked to rare neurological syndromes, episodic ataxia type 1 (EA1) and myokymia. In 2009, a KCNA1 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 (Mg2+) levels in these patients. In the present study, we describe a new de novo KCNA1 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 Mg2+ levels, renal Mg2+ wasting, muscle cramps, and tetanic episodes. Whole exome sequencing identified a p.Leu328Val mutation in KCNA1 encoding the Kv1.1 K+ 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 KCNA1 with hypomagnesemia, thereby emphasizing the need for further evaluation of the clinical phenotypes observed in patients carrying KCNA1 mutations.

Nur in Feld suchen:

Zuletzt gesuchte Begriffe: