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

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.

• Authors: Sara Locci, Rosanna Cardani, Paola Brunori, Sabrina Lucchiari, Giacomo P Comi, Antonio Federico, Nicola De Stefano, Giovanni Meola, Andrea Mignarri
• Journal: Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology (Neurol Sci) Vol. 42 Issue 12 Pg. 5365-5368 (Dec 2021) ISSN: 1590-3478 [Electronic] Italy
• PMID: 34386887 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2021. Fondazione Società Italiana di Neurologia.

Chemical References

• Chloride Channels
• DMPK protein, human
• Myotonin-Protein Kinase

Topics

• Chloride Channels (genetics)
• Hand Strength
• Humans
• Mutation
• Myotonia (genetics)
• Myotonia Congenita (complications, genetics)
• Myotonic Dystrophy (complications, genetics)
• Myotonin-Protein Kinase