A Compound Heterozygous Pathogenic Variant in Is Associated With Axonal Charcot-Marie-Tooth Disease

Overview

Journal J Clin Neurol

Specialty Neurology

Date 2021 Oct 1

PMID 34595861

Citations 4

Authors

Ji Man Hong

Hyeonjin Jeon

Young Chul Choi

Hanna Cho

Young Bin Hong

Hyung Jun Park

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Pathogenic variants in have been reported to cause hereditary spastic paraplegia 26. This study has revealed that a novel compound heterozygous pathogenic variant in is associated with axonal Charcot-Marie-Tooth disease (CMT).

Methods: Whole-exome sequencing (WES) was used to identify the causative factors and characterize the clinical features of a Korean family with sensorimotor polyneuropathy. Functional assessment of the mutant genes was performed using a motor neuron cell line.

Results: The WES revealed a compound heterozygous pathogenic variant (c.128dupC and c.451G>A) in as the causative of the present patient, a 53-year-old male who presented with axonal sensorimotor polyneuropathy and cognitive impairment without spasticity. The electrodiagnostic study showed axonal sensorimotor polyneuropathy. was critical to the proliferation of motor neuron cells. The compensation assay revealed that the pathogenic variants might affect the enzymatic activity of .

Conclusions: This study is the first to identify a case of autosomal recessive axonal CMT associated with a compound heterozygous pathogenic variant in . This finding expands the clinical and genetic spectra of peripheral neuropathy.

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