Abstract
Paramyotonia congenita is a non-dystrophic myotonia, in which muscle relaxation is delayed after voluntary or evoked contraction. This condition cannot be distinguished on the basis of symptoms and signs alone. It requires consideration of genetics as more than 100 mutations in the CLCN1 gene and at least 20 mutations in the SCN4A gene are associated with the clinical features of the non-dystrophic myotonias. Only a few families with the described features but no genetic testing have been reported in Slovakia. This prompted us to investigate genetic mutations in the SCN4A gene in 3 Slovak families clinically diagnosed with paramyotonia. Genomic DNA of the family members was extracted from peripheral blood and amplified by polymerase chain reaction. SCN4A variants were screened by Sanger sequencing. Our results revealed 2 potential disease-causing mutations present in the probands and affected family members - mutations c.3938C > T (p.T1313M) in two families and mutation c.2111C>T (p. T704M) in one family. Our results may help to identify genetic determinants as well as clarify genotype-phenotype relationships in patients with paramyotonia in Slovakia.
Highlights
Paramyotonia congenita (PMC) is an autosomal dominant disorder with paradoxical myotonia, defined as increased stiffness on repeated activities, and cold-induced muscle stiffness[1]
In Family 1 the mutation is associated with classic characteristics of PMC: exercise-induced muscle stiffness as well as intermittent periods of weakness not necessarily related to cold or myotonia
The mutation c.3938C>T (p.T1313M), which is the most frequently reported mutation in literature, was present in 2 of our families. This mutation is located in the DIII–DIV linker and is associated with classic characteristics of PMC: cold– and exercise-induced muscle stiffness as well as intermittent periods of weakness not necessarily related to cold or myotonia[12,13]
Summary
Paramyotonia congenita (PMC) is an autosomal dominant disorder with paradoxical myotonia, defined as increased stiffness on repeated activities, and cold-induced muscle stiffness[1]. Diseases caused by SCN4A mutations have diverse clinical phenotypes, PMC, and sodium channel myotonia, hyperkalemic and hypokalemic periodic paralysis, potassium-aggravated myotonia, and congenital myasthenia syndrome[4]. Paramyotonia congenita is a non-dystrophic myotonia, in which muscle relaxation is delayed after voluntary or evoked contraction This condition cannot be distinguished on the basis of symptoms and signs alone. It requires consideration of genetics as more than 100 mutations in the CLCN1 gene and at least 20 mutations in the SCN4A gene are associated with the clinical features of the non-dystrophic myotonias. A few families with the described features but no genetic testing have been reported in Slovakia This prompted us to investigate genetic mutations in the SCN4A gene in 3 Slovak families clinically diagnosed with paramyotonia.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
