# Novel Biallelic PLEKHG5 Variant Associated With Intermediate Charcot‐Marie‐Tooth Disease: Case Report From South America

## TL;DR

A new case of a genetic disorder linked to a PLEKHG5 variant is reported in South America, expanding the known range of this condition.

## Contribution

The study reports the first South American case of a PLEKHG5 variant associated with intermediate Charcot-Marie-Tooth disease.

## Key findings

- A male patient from South America was found to have a homozygous PLEKHG5 variant (c.59G>A) associated with intermediate Charcot-Marie-Tooth disease.
- The patient exhibited clinical features consistent with intermediate Charcot-Marie-Tooth disease, including foot drop and motor conduction delays.
- This case expands the geographic and phenotypic spectrum of PLEKHG5-related neuropathies.

## Abstract

Biallelic pathogenic variants in PLEKHG5 are associated with two distinct recessive phenotypes, including distal hereditary motor neuropathy AR type 4 and intermediate Charcot‐Marie‐Tooth disease type C (CMT). No South American cases have been previously reported.

We evaluated a male patient with suspected hereditary neuropathy using clinical, electrophysiological, and genetic studies.

Symptoms began at 12 years with progressive distal weakness. At 40 years, he had foot drop, pes cavus, distal atrophy, areflexia, and sensory loss to the knees. Disability scales indicated moderate impairment. Electroneuromyography revealed abolished responses in the lower limbs and motor conduction velocities in the intermediate range (35–40 m/s). Genetic analysis identified the homozygous variant c.59G>A (p.Arg20Gln) in PLEKHG5, currently classified as VUS.

This reports presents a case from South American linking a homozygous PLEKHG5 variant to recessive intermediate CMT, expanding the geographic and phenotypic spectrum of PLEKHG5‐related neuropathies.