Request Demo

Last update 08 May 2025

Charcot-Marie-Tooth Disease, Type 4C

Last update 08 May 2025

Basic Info

Synonyms

CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, AUTOSOMAL RECESSIVE, TYPE 4C, CHARCOT-MARIE-TOOTH DISEASE, TYPE 4C, CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 4C

+ [11]

Introduction

An autosomal recessive form of demyelinating Charcot-Marie-Tooth disease caused by mutations in the SH3TC2 gene, encoding SH3 domain and tetratricopeptide repeat-containing protein 2.

Clinical Trials associated with Charcot-Marie-Tooth Disease, Type 4C

NCT05902351

/ RecruitingNot Applicable

Global Registry for Inherited Neuropathies Natural History Study for Charcot Marie Tooth Disease

The goal of this Natural History Study for Charcot-Marie-Tooth is to acquire, record, and analyze patient-reported data and associated genetic reports, Electronic Health Records (EHRs) and clinical notes to identify the burden, diagnostic journey, and prevalence of disease that will aid scientists in their work toward finding a cure.
Participants will be asked to complete a Natural History Survey.

Start Date01 Nov 2013

Sponsor / Collaborator

Hereditary Neuropathy Foundation, Inc.

NCT01193075

/ RecruitingNot ApplicableIIT

Natural History Evaluation of Charcot Marie Tooth Disease (CMT) Type (CMT1B), 2A (CMT2A), 4A (CMT4A), 4C (CMT4C), and Others

This is an observational longitudinal study to determine the natural history and genotype-phenotype correlations of disease causing mutations in Charcot Marie Tooth disease (CMT) type 1B (CMT1B), 2A (CMT2A), 4A (CMT4A), and 4C (CMT4C).
The investigators will also be determine the capability of the newly developed CMT Pediatric Scale (CMT Peds scale) and the Minimal Dataset to measure impairment and perform longitudinal measurements in patients with multiple forms of CMT over a five year window

Start Date01 Apr 2010

Sponsor / Collaborator

University of Iowa

[+19]

100 Clinical Results associated with Charcot-Marie-Tooth Disease, Type 4C

100 Translational Medicine associated with Charcot-Marie-Tooth Disease, Type 4C

0 Patents (Medical) associated with Charcot-Marie-Tooth Disease, Type 4C

Literatures (Medical) associated with Charcot-Marie-Tooth Disease, Type 4C

01 Jun 2025·Cellular Signalling

Two novel SH3TC2 mutations predispose to Charcot-Marie-Tooth disease type 4C by mistargeting away from TFRC

Article

Author: Li, Jianwei ; Wu, Changxin ; Zhang, Yanping ; Deng, Zhanjin ; Wu, Ya ; Xiong, Qiuhong ; Samad, Abdus ; Xi, Yuqian ; Li, Ping ; Song, Jiawen ; Zhou, Yong-An

Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive form of demyelinating neuropathy caused by the biallelic pathogenic mutations in the SH3TC2 gene and characterized by progressive scoliosis, muscular atrophy, distal weakness, and reduced nerve conduction velocity. Here, we report two novel SH3TC2 mutations (c.452dupT and c.731 + 1G > T) from a proband with typical clinical manifestations of CMT4C. Splicing assay reveals the SH3TC2 c.731 + 1G > T mutation leads to a 58-nucleotide (nt) deletion from the downstream of exon 6 causing a frameshift and resulting in an early termination of protein expression. Protein expression assay indicates SH3TC2 c.452dupT mutant is degraded by both the nonsense mediated decay (NMD) and the ubiquitin-proteasome pathway. Moreover, our intracellular immunofluorescence, co-immunoprecipitation, liquid chromatography mass spectrometry and molecular docking describe that SH3TC2 interacts with the transferrin receptor protein 1 (TFRC) encoding a cell surface receptor playing a crucial role in mediating iron homeostasis. Interestingly, both the two novel SH3TC2 mutations present in our CMT4C patients are defective in the association with TFRC. Our study reveals the pathogenesis of these two novel SH3TC2 mutations and indicates that the SH3TC2-TFRC interaction is relevant for peripheral nerve pathophysiology, thus provides a novel insight into the pathophysiology of CMT4C neuropathy.

01 Jun 2025·European Journal of Cell Biology

Advances in modeling the Charcot-Marie-Tooth disease: Human induced pluripotent stem cell-derived Schwann cells harboring SH3TC2 variants

Article

Author: Nizou, Angélique ; Pyromali, Ioanna ; Sturtz, Franck ; Rovini, Amandine ; Loret, Camille ; Faye, Pierre-Antoine ; Scherrer, Camille ; Lia, Anne-Sophie ; Favreau, Frédéric

Human induced pluripotent stem cells (hiPSCs) represent a powerful tool for investigating neuropathological disorders, such as Charcot-Marie-Tooth disease (CMT), the most prevalent inherited peripheral neuropathy, where the cells of interest are hardly accessible. Advancing the development of appropriate cellular models is crucial for studying the disease's pathophysiology. In this study, we present the first two isogenic hiPSC-derived Schwann cell models for studying CMT4C, also known as AR-CMTde-SH3TC2. This subtype of CMT is associated with alterations in SH3TC2 and is the most prevalent form of autosomal recessive demyelinating CMT. We aimed to study the impact of two nonsense mutations in SH3TC2. To achieve this, we used two CRISPR hiPSC clones, one carrying a homozygous nonsense mutation: c.211C>T, p.Gln71*, and the other one, carrying the most common AR-CMTde-SH3TC2 alteration, c.2860G>A, p.Arg954*. To study the endogenous expression of SH3TC2 in the cells mainly altered in AR-CMTde-SH3TC2, we initiated the differentiation of both our CMT clones and their isogenic control into Schwann cells (SCs). This study represents the first in vitro investigation of human endogenous SH3TC2 expression in AR-CMTde-SH3TC2 hiPSC-derived SC models, allowing for the examination of its expression and of its cellular impact. By comparing this AR-CMTde-SH3TC2 models to the control one, we observed disparities in RNA and protein expression of SH3TC2. Additionally, our RNA and coculture experiments with hiPSC-derived motor neurons (MNs) revealed delayed maturation of SCs and a reduced ability of SH3TC2-deficient SCs to sustain motor neuron culture. Our findings also demonstrated a disability in receptor recycling in SH3TC2-deficient cells, depending on the AR-CMTde-SH3TC2 alteration. These hiPSC-derived-SC models further provide a new modelling tool for studying Schwann cell contribution to CMT4C.

10 Mar 2025·Laboratory Medicine

Trigeminal neuralgia, demyelinating polyneuropathy, and central nervous system involvement in a patient with an SH3TC2 mutation

Article

Author: Pepe, Georgia ; Giannakis, Alexandros ; Sarmas, Ioannis ; Sidiropoulos, Christos ; Konitsiotis, Spiridon ; Chamko, Gkirai

AbstractBackgroundCharcot-Marie-Tooth type 4C (CMT4C) is a slowly progressive, autosomal recessive, sensorimotor polyneuropathy characterized by demyelination and distinct clinical features, including cranial nerve involvement. CMT4C is associated with pathogenic mutations in the SH3TC2 gene.MethodsA patient presenting with gait instability due to demyelinating polyneuropathy and refractory trigeminal neuralgia underwent comprehensive evaluation. Nerve conduction studies, magnetic resonance imaging (MRI) of the brain, cervical spine, and thoracic spine, lumbar puncture, and genetic test through next generation sequencing were performed.ResultsThe genetic test found an Arg1109Stop mutation in the SH3TC2 gene, associated with demyelinating polyneuropathy and cranial neuropathy. Interestingly, brain MRI showed multiple, nonenhancing white matter hyperintensities. This is the first case of CMT4C associated with white matter lesions.ConclusionAny patient with slowly progressive peripheral nervous system symptoms and disproportionally abnormal nerve conduction study findings should be tested for an inherited polyneuropathy and brain imaging for screening of possible central nervous system involvement should be performed. Further investigation is needed to elucidate the pathogenetic basis of CMT4C and a possible association with white matter lesions.

Analysis

Perform a panoramic analysis of this field.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Charcot-Marie-Tooth Disease, Type 4C

Basic Info

Related

Analysis