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

IF 3 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System Pub Date : 2026-01-21 DOI:10.1111/jns.70099

Rafael Oliveira Vidon, Pedro José Tomaselli, Caroline Bittar-Braune, Izabela Jardim Pitta, Glenda Corrêa Borges de Lacerda, Márcia Jardim

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引用次数: 0

Abstract

Background and Aims

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.

Methods

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

Results

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.

Interpretation

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.

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新的双等位基因PLEKHG5变异与中间腓骨肌病相关：来自南美的病例报告。

背景和目的：PLEKHG5的双等位致病变异与两种不同的隐性表型相关，包括远端遗传性运动神经病变AR 4型和中间charco - marie - tooth病C型（CMT）。南美洲以前没有报告病例。方法：我们通过临床、电生理和遗传学研究评估了一位疑似遗传性神经病变的男性患者。结果：症状开始于12岁，伴有进行性远端无力。40岁时，他出现足下垂、足弓足、远端萎缩、反射屈曲和膝盖感觉丧失。残疾量表显示中度损伤。神经肌电图显示下肢反应消失，运动传导速度在中间范围（35-40 m/s）。遗传分析鉴定出PLEKHG5的纯合变异c.59G>A (p.a arg20gln)，目前归类为VUS。解释：本报告提出了一个来自南美的病例，将PLEKHG5纯合子变异与隐性中间CMT联系起来，扩大了PLEKHG5相关神经病的地理和表型谱。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of the Peripheral Nervous System 医学-临床神经学

CiteScore

6.10

自引率

7.90%

发文量

审稿时长

>12 weeks

期刊介绍： The Journal of the Peripheral Nervous System is the official journal of the Peripheral Nerve Society. Founded in 1996, it is the scientific journal of choice for clinicians, clinical scientists and basic neuroscientists interested in all aspects of biology and clinical research of peripheral nervous system disorders. The Journal of the Peripheral Nervous System is a peer-reviewed journal that publishes high quality articles on cell and molecular biology, genomics, neuropathic pain, clinical research, trials, and unique case reports on inherited and acquired peripheral neuropathies. Original articles are organized according to the topic in one of four specific areas: Mechanisms of Disease, Genetics, Clinical Research, and Clinical Trials. The journal also publishes regular review papers on hot topics and Special Issues on basic, clinical, or assembled research in the field of peripheral nervous system disorders. Authors interested in contributing a review-type article or a Special Issue should contact the Editorial Office to discuss the scope of the proposed article with the Editor-in-Chief.