Predominantly myalgic phenotype caused by the c.3466G > A p.A1156T mutation in SCN4A gene

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http://hdl.handle.net/10138/183443

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Palmio , J , Sandell , S , Hanna , M G , Mannikko , R , Penttila , S & Udd , B 2017 , ' Predominantly myalgic phenotype caused by the c.3466G > A p.A1156T mutation in SCN4A gene ' , Neurology , vol. 88 , no. 16 , pp. 1520-1527 . https://doi.org/10.1212/WNL.0000000000003846

Title: Predominantly myalgic phenotype caused by the c.3466G > A p.A1156T mutation in SCN4A gene
Author: Palmio, Johanna; Sandell, Satu; Hanna, Michael G.; Mannikko, Roope; Penttila, Sini; Udd, Bjarne
Contributor organization: Department of Medical and Clinical Genetics
Medicum
Date: 2017-04-18
Language: eng
Number of pages: 8
Belongs to series: Neurology
ISSN: 0028-3878
DOI: https://doi.org/10.1212/WNL.0000000000003846
URI: http://hdl.handle.net/10138/183443
Abstract: Objective: To characterize the clinical phenotype in patients with p.A1156T sodium channel mutation. Methods: Twenty-nine Finnish patients identified with the c.3466G>A p.A1156T mutation in the SCN4A gene were extensively examined. In a subsequent study, 63 patients with similar myalgic phenotype and with negative results in myotonic dystrophy type 2 genetic screening (DM2-neg group) and 93 patients diagnosed with fibromyalgia were screened for the mutation. Functional consequences of the p.A1156T mutation were studied in HEK293 cells with whole-cell patch clamp. Results: The main clinical manifestation in p.A1156T patients was not myotonia or periodic paralysis but exercise-and cold-induced muscle cramps, muscle stiffness, and myalgia. EMG myotonic discharges were detected in most but not all. Electrophysiologic compound muscle action potentials exercise test showed variable results. The p.A1156T mutation was identified in one patient in the DM2-neg group but not in the fibromyalgia group, making a total of 30 patients so far identified. Functional studies of the p.A1156T mutation showed mild attenuation of channel fast inactivation. Conclusions: The unspecific symptoms of myalgia stiffness and exercise intolerance without clinical myotonia or periodic paralysis in p.A1156T patients make the diagnosis challenging. The symptoms of milder SCN4A mutations may be confused with other similar myalgic syndromes, including fibromyalgia and myotonic dystrophy type 2.
Subject: SODIUM-CHANNEL MUTATIONS
PERIODIC PARALYSIS
MUSCLE BIOPSY
MYOTONIA
COLD
ELECTROMYOGRAPHY
INACTIVATION
CHANNELOPATHIES
DISORDERS
FAMILIES
3124 Neurology and psychiatry
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: publishedVersion


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