University of Oulu

Phenotype of Patients With Charcot-Marie-Tooth With the p.His123Arg Mutation in GDAP1 in Northern Finland Maria Lehtilahti, Mika Kallio, Kari Majamaa, Mikko Kärppä Neurol Genet Dec 2021, 7 (6) e629; DOI: 10.1212/NXG.0000000000000629

Phenotype of patients with Charcot-Marie-Tooth with the p.His123Arg mutation in GDAP1 in northern Finland

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Author: Lehtilahti, Maria1,2,3; Kallio, Mika4,5; Majamaa, Kari1,2,3;
Organizations: 1Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
2Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland
3Department of Neurology, Oulu University Hospital, Oulu, Finland
4Department of Clinical Neurophysiology, Medical Research Center Oulu, Oulu University Hospital, Finland
5Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
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Language: English
Published: Wolters Kluwer, 2021
Publish Date: 2022-02-16


Background and Objectives: Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene cause autosomal dominant or autosomal recessive forms of Charcot-Marie-Tooth disease (CMT). Our aim was to study the clinical phenotype of patients with CMT caused by heterozygous p.His123Arg in GDAP1.

Methods: Twenty-three Finnish patients were recruited from a population-based cohort and through family investigation. Each patient was examined clinically and electrophysiologically. The Neuropathy Symptom Score and the Neuropathy Disability Score (NDS) were used in clinical evaluation.

Results: The median age at onset of symptoms was 17 years among patients with p.His123Arg in GDAP1. Motor symptoms were markedly more common than sensory symptoms at onset. All patients had distal weakness in lower extremities, and 17 (74%) patients had proximal weakness. Muscle atrophy and pes cavus were also common. Nineteen (82%) patients had sensory symptoms such as numbness or pain. The disease progressed with age, and the NDS increased 8.5 points per decade. Electrodiagnostic testing revealed length-dependent, sensory and motor axonal polyneuropathy. EDx findings were asymmetrical in 14 patients. Genealogic study of the families suggested a founder effect.

Discussion: We found that CMT in patients with p.His123Arg in GDAP1 is relatively mild and slow in progression.

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Series: Neurology. Genetics
ISSN: 2376-7839
ISSN-E: 2376-7839
ISSN-L: 2376-7839
Volume: 7
Issue: 6
Article number: e629
DOI: 10.1212/NXG.0000000000000629
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
3111 Biomedicine
Funding: Grants from the Finnish Brain Foundation, Finnish Medical Foundation, Medical Research Center, University of Oulu, and Oulu University Hospital.
Copyright information: © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.