Co-Existing Charcot-Marie-Tooth Disease Type II and Parkinson’s Disease Linked to a Novel DNAjB2 Pathogenic Variant

TL;DR

A rare case links a DNAjB2 gene mutation to both Charcot-Marie-Tooth disease and Parkinson’s disease, suggesting a shared genetic cause.

Contribution

This is the first report of dual CMT2 and young-onset PD linked to compound heterozygous DNAjB2 variants.

Findings

Compound heterozygous DNAjB2 variants were found in a patient with CMT2 and PD.

DNAjB2 dysfunction may cause neurodegeneration in both peripheral and central nervous systems.

Abstract

The DNAjB2 gene encodes a co-chaperone protein that interacts with the heat shock protein (HSP) family to maintain protein quality control and preserve neuronal integrity. Variants in this gene have been associated with the axonal form of Charcot-Marie-Tooth Disease (CMT2). Recent literature has also suggested an association between DNAjB2 variants and neurodegenerative disorders such as Parkinson’s disease (PD).

Case Report.

We present a 36-year-old female patient initially diagnosed with CMT2 at the age of 28, who later developed symptoms of PD in her fourth decade. Genetic test revealed compound heterozygous pathogenic variants in DNAjB2 (c.352+1 G>A and c.175+2T>A).

To our knowledge, this is the first case report describing the dual phenotype of CMT2 and young-onset PD linked to compound heterozygosity in DNAjB2. The dual dysfunction of axonal degeneration and dopaminergic neuron loss suggests that DNAjB2 plays a pivotal role in maintaining proteostasis in both the peripheral and central nervous systems.

This case report discusses a rare case of a 36-year-old female diagnosed with Charcot-Marie-Tooth (CMT) type 2 disease who later developed Parkinson's disease (PD). A few other family members were diagnosed with CMT and PD. Her genetic testing revealed a mutation in the DNAjB2 gene. The DANjB2 gene is essential for maintaining healthy proteins in both the central and peripheral nervous systems. Dysfunction of this gene leads to neurodegeneration and the development of CMT (peripheral) and PD (central). This gene could be a potential therapeutic target for such overlapping clinical phenotypes.

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