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The dominant chloride channel mutant G200R causing fluctuating myotonia: Clinical findings, electrophysiology, and channel pathology
Author(s) -
Wagner Susanne,
Deymeer Feza,
Kürz Lothar L.,
Benz Sandra,
Schleithoff Lothar,
LehmannHorn Frank,
Serdaroğlu Piraye,
Özdemir Coskun,
Rüdel Reinhardt
Publication year - 1998
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/(sici)1097-4598(199809)21:9<1122::aid-mus2>3.0.co;2-9
Subject(s) - myotonia , channelopathy , myotonia congenita , mutant , sodium channel , medicine , potassium channel , mutation , endocrinology , chemistry , biochemistry , sodium , gene , organic chemistry , myotonic dystrophy
Clinical, electrophysiological, and molecular findings are reported for a family with dominant myotonia congenita in which all affected members have experienced long‐term fluctuations of the symptom of myotonia. In some patients myotonia is combined with myalgia. The myotonia‐causing mutation in this family is in the gene encoding the muscular chloride channel, hClC‐1, predicting the amino acid exchange G200R. We have constructed recombinant DNA vectors for expression of the mutant protein in tsA201 cells and investigation of the properties of the mutant channel. The most prominent alteration was a +100‐mV shift of the midpoint of the activation curve. Therefore, within the physiological range the open probability of the mutant channel is markedly smaller than in wild‐type. This shift is likely to be responsible for the myotonia in the patients. The fluctuating symptoms of this chloride channelopathy are discussed with respect to short‐term fluctuations of myotonia in the sodium channelopathy of potassium‐aggravated myotonia. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1122–1128, 1998.