Abstract
A patient with an early severe myotonia diagnosed for Myotonic Dystrophy type 2 (DM2) was found bearing the combined effects of DM2 mutation and Nav1.4 S906T substitution. To investigate the mechanism underlying his atypical phenotype,whole-cell patch-clamp in voltage- and current-clamp mode was performed in myoblasts and myotubes obtained from his muscle biopsy. Results characterizing the properties of the sodium current and of the action potentials have been compared to those obtained in muscle cells derived from his mother, also affected by DM2, but without the S906T polymorphism. A faster inactivation kinetics and a +5 mV shift in the availability curve were found in the sodium current recorded in patient’s myoblasts compared to his mother. 27% of his myotubes displayed spontaneous activity. Patient’s myotubes showing a stable resting membrane potential had a lower rheobase current respect to the mother’s while the overshoot and the maximum slope of the depolarizing phase of action potential were higher. These findings suggest that SCN4A polymorphisms may be responsible for a higher excitability of DM2 patients sarcolemma, supporting the severe myotonic phenotype observed. We suggest SCN4A as a modifier factor and that its screening should be performed in DM2 patients with uncommon clinical features.
| Original language | English |
|---|---|
| Article number | 11058 |
| Journal | Scientific Reports |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Dec 1 2018 |
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ASJC Scopus subject areas
- General
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SCN4A as modifier gene in patients with myotonic dystrophy type 2. / Binda, Anna; Renna, Laura V.; Bosè, Francesca; Brigonzi, Elisa; Botta, Annalisa; Valaperta, Rea; Fossati, Barbara; Rivolta, Ilaria; Meola, Giovanni; Cardani, Rosanna.
In: Scientific Reports, Vol. 8, No. 1, 11058, 01.12.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - SCN4A as modifier gene in patients with myotonic dystrophy type 2
AU - Binda, Anna
AU - Renna, Laura V.
AU - Bosè, Francesca
AU - Brigonzi, Elisa
AU - Botta, Annalisa
AU - Valaperta, Rea
AU - Fossati, Barbara
AU - Rivolta, Ilaria
AU - Meola, Giovanni
AU - Cardani, Rosanna
PY - 2018/12/1
Y1 - 2018/12/1
N2 - A patient with an early severe myotonia diagnosed for Myotonic Dystrophy type 2 (DM2) was found bearing the combined effects of DM2 mutation and Nav1.4 S906T substitution. To investigate the mechanism underlying his atypical phenotype,whole-cell patch-clamp in voltage- and current-clamp mode was performed in myoblasts and myotubes obtained from his muscle biopsy. Results characterizing the properties of the sodium current and of the action potentials have been compared to those obtained in muscle cells derived from his mother, also affected by DM2, but without the S906T polymorphism. A faster inactivation kinetics and a +5 mV shift in the availability curve were found in the sodium current recorded in patient’s myoblasts compared to his mother. 27% of his myotubes displayed spontaneous activity. Patient’s myotubes showing a stable resting membrane potential had a lower rheobase current respect to the mother’s while the overshoot and the maximum slope of the depolarizing phase of action potential were higher. These findings suggest that SCN4A polymorphisms may be responsible for a higher excitability of DM2 patients sarcolemma, supporting the severe myotonic phenotype observed. We suggest SCN4A as a modifier factor and that its screening should be performed in DM2 patients with uncommon clinical features.
AB - A patient with an early severe myotonia diagnosed for Myotonic Dystrophy type 2 (DM2) was found bearing the combined effects of DM2 mutation and Nav1.4 S906T substitution. To investigate the mechanism underlying his atypical phenotype,whole-cell patch-clamp in voltage- and current-clamp mode was performed in myoblasts and myotubes obtained from his muscle biopsy. Results characterizing the properties of the sodium current and of the action potentials have been compared to those obtained in muscle cells derived from his mother, also affected by DM2, but without the S906T polymorphism. A faster inactivation kinetics and a +5 mV shift in the availability curve were found in the sodium current recorded in patient’s myoblasts compared to his mother. 27% of his myotubes displayed spontaneous activity. Patient’s myotubes showing a stable resting membrane potential had a lower rheobase current respect to the mother’s while the overshoot and the maximum slope of the depolarizing phase of action potential were higher. These findings suggest that SCN4A polymorphisms may be responsible for a higher excitability of DM2 patients sarcolemma, supporting the severe myotonic phenotype observed. We suggest SCN4A as a modifier factor and that its screening should be performed in DM2 patients with uncommon clinical features.
UR - http://www.scopus.com/inward/record.url?scp=85050608480&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050608480&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-29302-z
DO - 10.1038/s41598-018-29302-z
M3 - Article
C2 - 30038349
AN - SCOPUS:85050608480
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 11058
ER -