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. 2021 Oct 5;7(6):e629.
doi: 10.1212/NXG.0000000000000629. eCollection 2021 Dec.

Phenotype of Patients With Charcot-Marie-Tooth With the p.His123Arg Mutation in GDAP1 in Northern Finland

Maria Lehtilahti  1 , Mika Kallio  1 , Kari Majamaa  1 , Mikko Kärppä  1
Affiliations

Phenotype of Patients With Charcot-Marie-Tooth With the p.His123Arg Mutation in GDAP1 in Northern Finland

Maria Lehtilahti et al. Neurol Genet. .

Abstract

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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Figures

Figure 1
Figure 1. Cumulative Incidence of Polyneuropathy in the Pedigrees of 23 Patients With the p.His123Arg in GDAP1
Subjects were censored at current age or at death.
Figure 2
Figure 2. Birthplaces of Ancestors in 8 Pedigrees With the p.His123Arg in GDAP1 Placed on a Map of Finland
The province of Northern Ostrobothnia is the shaded area.
See this image and copyright information in PMC

References

    1. Pipis M, Rossor AM, Laura M, Reilly MM. Next-generation sequencing in Charcot-Marie-Tooth disease: opportunities and challenges. Nat Rev Neurol. 2019;15(11):644-656. - PubMed
    1. Cuesta A, Pedrola L, Sevilla T, et al. . The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease. Nat Genet. 2002;30(1):22-25. - PubMed
    1. Pezzini I, Geroldi A, Capponi S, et al. . GDAP1 mutations in Italian axonal Charcot-Marie-Tooth patients: phenotypic features and clinical course. Neuromuscul Disord. 2016;26(1):26-32. - PubMed
    1. Sivera R, Frasquet M, Lupo V, et al. . Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain. Sci Rep. 2017;7(1):6677. - PMC - PubMed
    1. Yoshimura A, Yuan JH, Hashiguchi A, et al. . Clinical and mutational spectrum of Japanese patients with Charcot-Marie-Tooth disease caused by GDAP1 variants. Clin Genet. 2017;92(3):274-280. - PubMed