Supplementary Material for: A de novo <b><i>KCNA1</i></b> Mutation in a Patient with Tetany and Hypomagnesemia
van der Wijst J.
Konrad M.
Verkaart S.A.J.
Tkaczyk M.
Latta F.
Altmüller J.
Thiele H.
Beck B.
Schlingmann K.P.
de Baaij J.H.F.
10.6084/m9.figshare.6324815.v1
https://karger.figshare.com/articles/dataset/Supplementary_Material_for_A_de_novo_b_i_KCNA1_i_b_Mutation_in_a_Patient_with_Tetany_and_Hypomagnesemia/6324815
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.
2018-05-23 11:26:50
Magnesium
Potassium channel
Genetics
Patch clamp
Hypomagnesemia