Evidence map›Paper›PMID 27164696›Full record

ArticleNeurology2016

Translational approach to address therapy in myotonia permanens due to a new SCN4A mutation.

Jean-François Desaphy, Roberta Carbonara, Adele D'Amico, Anna Modoni, Julien Roussel, Paola Imbrici, Serena Pagliarani, Sabrina Lucchiari, Mauro Lo Monaco, Diana Conte Camerino

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PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Pharmacological therapy of non-dystrophic myotonias.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2025
    Review
  4. Preclinical study of the antimyotonic efficacy of safinamide in the myotonic mouse model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024
    Article
  5. Article
  6. Blockers of Skeletal Muscle NaInternational journal of molecular sciences · 2023
    Review
  7. Review
  8. Review
  9. Treatment Updates for Neuromuscular Channelopathies.Current treatment options in neurology · 2020
    Review
  10. Article
  11. Article
  12. Article
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Jean-François DesaphyFrom the Departments of Biomedical Sciences and Human Oncology (J.-F.D.) and Pharmacy & Drug Sciences (R.C., J.R., P.I., D.C.C.), University of Bari Aldo Moro, Bari; Unit of Neuromuscular and Neurodegenerative Disorders (A.D.), Bambino Gesù Children's Hospital, Rome; Departments of Geriatrics, Neurosciences, and Orthopedics (A.M., M.L.M.), Institute of Neurology, Catholic University of the Sacred Heart, Rome; Dino Ferrari Centre (S.P., S.L.), Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan; and Neurology Unit (S.P., S.L.), IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. jeanfrancois.desaphy@uniba.it.
Roberta CarbonaraFrom the Departments of Biomedical Sciences and Human Oncology (J.-F.D.) and Pharmacy & Drug Sciences (R.C., J.R., P.I., D.C.C.), University of Bari Aldo Moro, Bari; Unit of Neuromuscular and Neurodegenerative Disorders (A.D.), Bambino Gesù Children's Hospital, Rome; Departments of Geriatrics, Neurosciences, and Orthopedics (A.M., M.L.M.), Institute of Neurology, Catholic University of the Sacred Heart, Rome; Dino Ferrari Centre (S.P., S.L.), Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan; and Neurology Unit (S.P., S.L.), IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Adele D'AmicoFrom the Departments of Biomedical Sciences and Human Oncology (J.-F.D.) and Pharmacy & Drug Sciences (R.C., J.R., P.I., D.C.C.), University of Bari Aldo Moro, Bari; Unit of Neuromuscular and Neurodegenerative Disorders (A.D.), Bambino Gesù Children's Hospital, Rome; Departments of Geriatrics, Neurosciences, and Orthopedics (A.M., M.L.M.), Institute of Neurology, Catholic University of the Sacred Heart, Rome; Dino Ferrari Centre (S.P., S.L.), Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan; and Neurology Unit (S.P., S.L.), IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Anna ModoniFrom the Departments of Biomedical Sciences and Human Oncology (J.-F.D.) and Pharmacy & Drug Sciences (R.C., J.R., P.I., D.C.C.), University of Bari Aldo Moro, Bari; Unit of Neuromuscular and Neurodegenerative Disorders (A.D.), Bambino Gesù Children's Hospital, Rome; Departments of Geriatrics, Neurosciences, and Orthopedics (A.M., M.L.M.), Institute of Neurology, Catholic University of the Sacred Heart, Rome; Dino Ferrari Centre (S.P., S.L.), Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan; and Neurology Unit (S.P., S.L.), IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Julien RousselFrom the Departments of Biomedical Sciences and Human Oncology (J.-F.D.) and Pharmacy & Drug Sciences (R.C., J.R., P.I., D.C.C.), University of Bari Aldo Moro, Bari; Unit of Neuromuscular and Neurodegenerative Disorders (A.D.), Bambino Gesù Children's Hospital, Rome; Departments of Geriatrics, Neurosciences, and Orthopedics (A.M., M.L.M.), Institute of Neurology, Catholic University of the Sacred Heart, Rome; Dino Ferrari Centre (S.P., S.L.), Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan; and Neurology Unit (S.P., S.L.), IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Paola ImbriciFrom the Departments of Biomedical Sciences and Human Oncology (J.-F.D.) and Pharmacy & Drug Sciences (R.C., J.R., P.I., D.C.C.), University of Bari Aldo Moro, Bari; Unit of Neuromuscular and Neurodegenerative Disorders (A.D.), Bambino Gesù Children's Hospital, Rome; Departments of Geriatrics, Neurosciences, and Orthopedics (A.M., M.L.M.), Institute of Neurology, Catholic University of the Sacred Heart, Rome; Dino Ferrari Centre (S.P., S.L.), Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan; and Neurology Unit (S.P., S.L.), IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Serena PagliaraniFrom the Departments of Biomedical Sciences and Human Oncology (J.-F.D.) and Pharmacy & Drug Sciences (R.C., J.R., P.I., D.C.C.), University of Bari Aldo Moro, Bari; Unit of Neuromuscular and Neurodegenerative Disorders (A.D.), Bambino Gesù Children's Hospital, Rome; Departments of Geriatrics, Neurosciences, and Orthopedics (A.M., M.L.M.), Institute of Neurology, Catholic University of the Sacred Heart, Rome; Dino Ferrari Centre (S.P., S.L.), Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan; and Neurology Unit (S.P., S.L.), IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Sabrina LucchiariFrom the Departments of Biomedical Sciences and Human Oncology (J.-F.D.) and Pharmacy & Drug Sciences (R.C., J.R., P.I., D.C.C.), University of Bari Aldo Moro, Bari; Unit of Neuromuscular and Neurodegenerative Disorders (A.D.), Bambino Gesù Children's Hospital, Rome; Departments of Geriatrics, Neurosciences, and Orthopedics (A.M., M.L.M.), Institute of Neurology, Catholic University of the Sacred Heart, Rome; Dino Ferrari Centre (S.P., S.L.), Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan; and Neurology Unit (S.P., S.L.), IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Mauro Lo MonacoFrom the Departments of Biomedical Sciences and Human Oncology (J.-F.D.) and Pharmacy & Drug Sciences (R.C., J.R., P.I., D.C.C.), University of Bari Aldo Moro, Bari; Unit of Neuromuscular and Neurodegenerative Disorders (A.D.), Bambino Gesù Children's Hospital, Rome; Departments of Geriatrics, Neurosciences, and Orthopedics (A.M., M.L.M.), Institute of Neurology, Catholic University of the Sacred Heart, Rome; Dino Ferrari Centre (S.P., S.L.), Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan; and Neurology Unit (S.P., S.L.), IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Diana Conte CamerinoFrom the Departments of Biomedical Sciences and Human Oncology (J.-F.D.) and Pharmacy & Drug Sciences (R.C., J.R., P.I., D.C.C.), University of Bari Aldo Moro, Bari; Unit of Neuromuscular and Neurodegenerative Disorders (A.D.), Bambino Gesù Children's Hospital, Rome; Departments of Geriatrics, Neurosciences, and Orthopedics (A.M., M.L.M.), Institute of Neurology, Catholic University of the Sacred Heart, Rome; Dino Ferrari Centre (S.P., S.L.), Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan; and Neurology Unit (S.P., S.L.), IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Ferrari (Italy) · ITUniversità Cattolica del Sacro Cuore · ITUniversity of Milan · ITUniversity of the Sacred Heart · JP

Funding

Telethon GGP14096
6 · The paper itself

Abstract

objectiveWe performed a clinical, functional, and pharmacologic characterization of the novel p.P1158L Nav1.4 mutation identified in a young girl presenting a severe myotonic phenotype.

methodsWild-type hNav1.4 channel and P1158L mutant were expressed in tsA201 cells for functional and pharmacologic studies using patch-clamp.

resultsThe patient shows pronounced myotonia, slowness of movements, and generalized muscle hypertrophy. Because of general discomfort with mexiletine, she was given flecainide with satisfactory response. In vitro, mutant channels show a slower current decay and a rightward shift of the voltage dependence of fast inactivation. The voltage dependence of activation and slow inactivation were not altered. Mutant channels were less sensitive to mexiletine, whereas sensitivity to flecainide was not altered. The reduced inhibition of mutant channels by mexiletine was also observed using clinically relevant drug concentrations in a myotonic-like condition.

conclusionsClinical phenotype and functional alterations of P1158L support the diagnosis of myotonia permanens. Impairment of fast inactivation is consistent with the possible role of the channel domain III S4-S5 loop in the inactivation gate docking site. The reduced sensitivity of P1158L to mexiletine may have contributed to the unsatisfactory response of the patient. The success of flecainide therapy underscores the usefulness of in vitro functional studies to help in the choice of the best drug for each individual.

Indexed as

MutationCell LineChildDiagnosis, DifferentialFemaleFlecainideHumansMexiletineMyotonia CongenitaNAV1.4 Voltage-Gated Sodium ChannelPharmacogenomic TestingPrecision MedicineTranslational Research, BiomedicalVoltage-Gated Sodium Channel BlockersFlecainideMexiletineNAV1.4 Voltage-Gated Sodium ChannelSCN4A protein, humanVoltage-Gated Sodium Channel Blockers

Identifiers

PMID27164696
PMCPMC4891212
OpenAlexW2344690225

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.