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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Archivio Istituziona...arrow_drop_down
image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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Clinical evaluation and cellular electrophysiology of a recessive CLCN1 patient.

Authors: S. Lucchiari; G. Ulzi; F. Magri; M. Bucchia; F. Corbetta; M. Servida; M. Moggio; +2 Authors

Clinical evaluation and cellular electrophysiology of a recessive CLCN1 patient.

Abstract

Here we present the case of a 32-year-old female patient with myotonia congenita. She carried two mutations in the CLCN1 gene that encodes the chloride channel ClC-1: p.Phe167Leu, which was previously identified in several families, and p.Val536Leu, which has been previously reported but not yet characterized by electrophysiological investigations. The patient's symptoms included generalized stiffness, myotonia, and muscle cramps mostly localized in the lower limbs. These symptoms started during childhood and worsened over the following years. The symptoms were exacerbated by low outside temperature, rest, stress, and fasting and were improved by mild exercise, suggesting a warm-up phenomenon. The mutation p.Phe167Leu has previously been associated with a slight shift in the overall open probability. Here we further analysed this mutation to extrapolate the voltage-dependence of the fast and slow gates. In our experimental conditions, p.Phe167Leu exclusively affected the slow gate, increasing the minimum open probability and displacing the voltage-dependence toward depolarized potentials. p.Val536Leu showed more severe effects, dramatically influencing the slow gate as well as modifying properties of the fast gate. Co-expression of the mutants in a human cell line to reproduce the compound heterozygous condition of the patient produced channels with altered voltage-dependence of the slow gate but a restored fast gate. The alteration of the slow mechanism was reflected by the relative open probability, reducing the contribution of ClC-1 channels in maintaining the resting membrane potential of skeletal muscles and thus explaining the myotonic phenotype of the patient.

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Italy
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Keywords

Adult; Cell Line; Chloride Channels; Female; Humans; Mutation; Myotonia Congenita, Adult, Myotonia Congenita, Chloride Channels, Mutation, Humans, Female, Cell Line

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
8
Average
Average
Average
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