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Locci S, Cardani R, Brunori P, et al. Co-occurrence of DMPK expansion and CLCN1 mutation in a patient with myotonia. Neurol Sci. 2021;42(12):5365-5368doi: 10.1007/s10072-021-05538-y.
Locci, S., Cardani, R., Brunori, P., Lucchiari, S., Comi, G. P., Federico, A., De Stefano, N., Meola, G., & Mignarri, A. (2021). Co-occurrence of DMPK expansion and CLCN1 mutation in a patient with myotonia. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 42(12), 5365-5368. https://doi.org/10.1007/s10072-021-05538-y
Locci, Sara, et al. "Co-occurrence of DMPK expansion and CLCN1 mutation in a patient with myotonia." Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology vol. 42,12 (2021): 5365-5368. doi: https://doi.org/10.1007/s10072-021-05538-y
Locci S, Cardani R, Brunori P, Lucchiari S, Comi GP, Federico A, De Stefano N, Meola G, Mignarri A. Co-occurrence of DMPK expansion and CLCN1 mutation in a patient with myotonia. Neurol Sci. 2021 Dec;42(12):5365-5368. doi: 10.1007/s10072-021-05538-y. Epub 2021 Aug 13. PMID: 34386887.
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Neurol Sci. 2021 Dec;42(12):5365-5368. doi: 10.1007/s10072-021-05538-y. Epub 2021 Aug 13.

Co-occurrence of DMPK expansion and CLCN1 mutation in a patient with myotonia.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

Sara Locci, Rosanna Cardani, Paola Brunori, Sabrina Lucchiari, Giacomo P Comi, Antonio Federico, Nicola De Stefano, Giovanni Meola, Andrea Mignarri

Affiliations

  1. Department of Medical, Surgical and Neurological Sciences, Unit of Neurology and Neurometabolic Diseases, University of Siena, Siena, Italy.
  2. Laboratory of Muscle Histopathology and Molecular Biology, IRCCS Policlinico San Donato, Milan, Italy.
  3. Unit of Neurophysiopathology, Silvestrini Hospital, Perugia, Italy.
  4. Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
  5. Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
  6. Department of Neurorehabilitation Sciences, Casa di Cura del Policlinico, Milan, Italy.
  7. Department of Medical, Surgical and Neurological Sciences, Unit of Neurology and Neurometabolic Diseases, University of Siena, Siena, Italy. [email protected].
  8. Department of Medicine, Surgery and Neurosciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy. [email protected].

PMID: 34386887 DOI: 10.1007/s10072-021-05538-y

Abstract

INTRODUCTION: Myotonic disorders are a group of diseases affecting the muscle, in different ways. Myotonic dystrophy type 1 (DM1) is related to (CTG)n expansion in the 3-untranslated region of the dystrophia myotonica protein kinase (DMPK) gene and is the most frequent and disabling form, causing muscular, visibility, respiratory, and cardiac impairment. Non-dystrophic myotonias (NDMs) affect the skeletal muscle alone. In particular, mutations in the chloride channel (CLCN1) gene cause myotonia congenita (MC), which can have autosomal dominant or recessive inheritance.

CASE REPORT: We describe a patient with a family history of asymptomatic or paucisymptomatic myotonia, who presented handgrip myotonia which sharply reduced after mexiletine administration. Molecular analysis showed both a paternally inherited DMPK expansion and a maternally inherited CLCN1 mutation.

CONCLUSIONS: Only one other similar case was reported so far; however, the segregation of the two mutations and the characteristics of the muscle were not studied. Since our patient lacked the classical phenotypical and muscle histopathological characteristics of DM1 and showed mild splicing alterations despite a pathogenic DMPK expansion and the nuclear accumulation of toxic RNA, we may speculate that the co-occurrence of a CLCN1 mutation could have attenuated the severity of DM1 phenotype.

© 2021. Fondazione Società Italiana di Neurologia.

Keywords: CLCN1; DMPK; Myotonia; Myotonia congenita; Myotonic dystrophy type 1

References

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