SCN4A as modifier gene in patients with myotonic dystrophy type 2

Anna Binda, Laura V. Renna, Francesca Bosè, Elisa Brigonzi, Annalisa Botta, Rea Valaperta, Barbara Fossati, Ilaria Rivolta, Giovanni Meola, Rosanna Cardani

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageEnglish
Article number11058
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

Fingerprint

Modifier Genes
Myotonic Dystrophy
Skeletal Muscle Fibers
Myoblasts
Mothers
Action Potentials
Sodium
Myotonia
Phenotype
Sarcolemma
Membrane Potentials
Muscle Cells
Biopsy
Muscles
Mutation

ASJC Scopus subject areas

  • General

Cite this

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 journalArticle

Binda, Anna ; Renna, Laura V. ; Bosè, Francesca ; Brigonzi, Elisa ; Botta, Annalisa ; Valaperta, Rea ; Fossati, Barbara ; Rivolta, Ilaria ; Meola, Giovanni ; Cardani, Rosanna. / SCN4A as modifier gene in patients with myotonic dystrophy type 2. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{9e15e42350cb43b59da77fef77ceaf80,
title = "SCN4A as modifier gene in patients with myotonic dystrophy type 2",
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.",
author = "Anna Binda and Renna, {Laura V.} and Francesca Bos{\`e} and Elisa Brigonzi and Annalisa Botta and Rea Valaperta and Barbara Fossati and Ilaria Rivolta and Giovanni Meola and Rosanna Cardani",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-29302-z",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

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 -