Related Experiment Video
Updated: Jul 11, 2025
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Clinical and genetic features of patients suffering from CMT4J
Sadia Beloribi-Djefaflia1,2, Raul Juntas Morales3, Farzad Fatehi1,2
1Reference Center for Neuromuscular Disorders and ALS, Timone University Hospital, Aix-Marseille University, 264 Rue Saint Pierre, 05 13385, Marseille, Cedex, France.
Abstract:
Mutations in the FIG4 gene have been identified in various diseases, including amyotrophic lateral sclerosis, Parkinson's disease, and Charcot-Marie-Tooth 4 J (CMT4J), with a wide range of phenotypic manifestations. We present eight cases of CMT4J patients carrying the p.Ile41Thr mutation of FIG4. The patients were categorized according to their phenotype. Six patients had a pure CMT; whereas, two patients had a CMT associated with parkinsonism. Three patients had an early onset and exhibited more severe forms of the disease. Three others experienced symptoms in their teenage years and had milder forms. Two patients had a late onset in adulthood. Four patients showed electrophysiological evidence of conduction blocks, typically associated with acquired neuropathies. Consequently, two of them received intravenous immunoglobulin treatment without a significant objective response. Interestingly, two heterozygous patients with the same mutations exhibited contrasting phenotypes, one having a severe early-onset form and the other experiencing a slow disease progression starting at the age of 49. Notably, although 7 out of 8 patients in this study were compound heterozygous for the p.Ile41Thr mutation, only one individual was found to be homozygous for this genetic variant and exhibited an early-onset, severe form of the disease. Additionally, one patient who developed the disease in his youth was also diagnosed with hereditary neuropathy with pressure palsies. Our findings provide insights into the CMT4J subtype by reporting on eight heterogeneous patient cases and highlight the potential for misdiagnosis when conduction blocks or asymmetrical nerve conduction study results are observed in patients with FIG4 mutations.
Insights
Mutations in the FIG4 gene cause Charcot-Marie-Tooth 4J (CMT4J), presenting diverse symptoms. This study details eight CMT4J cases, revealing variable disease severity and onset, and highlighting potential diagnostic challenges.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Mutations in the FIG4 gene are linked to neurodegenerative disorders, including Charcot-Marie-Tooth 4J (CMT4J).
- FIG4 mutations exhibit a broad spectrum of clinical presentations, complicating diagnosis and management.
- Understanding genotype-phenotype correlations is crucial for effective patient care.
Purpose of the Study:
- To investigate the phenotypic variability in eight patients with the p.Ile41Thr mutation in the FIG4 gene.
- To explore the clinical spectrum of Charcot-Marie-Tooth 4J (CMT4J) associated with specific FIG4 mutations.
- To identify potential diagnostic challenges and improve understanding of CMT4J.
Main Methods:
- Case series analysis of eight CMT4J patients carrying the FIG4 p.Ile41Thr mutation.
- Phenotypic categorization based on disease onset, severity, and associated symptoms (e.g., parkinsonism).
- Electrophysiological studies and genetic analysis (heterozygous and homozygous states).
Main Results:
- Eight CMT4J patients with the FIG4 p.Ile41Thr mutation showed diverse phenotypes, ranging from pure CMT to CMT with parkinsonism.
- Disease onset varied from early childhood to adulthood, correlating with severity.
- Electrophysiological findings like conduction blocks occurred in four patients, mimicking acquired neuropathies, and IVIg treatment was ineffective.
- Heterozygous patients displayed contrasting phenotypes, and one homozygous patient had a severe early-onset form.
Conclusions:
- The p.Ile41Thr mutation in FIG4 leads to a heterogeneous CMT4J phenotype with variable expressivity.
- Conduction blocks and asymmetrical nerve conduction study results in patients with FIG4 mutations may lead to misdiagnosis.
- Further research is needed to fully elucidate the complex genotype-phenotype relationships in CMT4J.
More Related Videos
09:37Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
06:35In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration
Published on: June 15, 2018
Related Concept Videos
01:33Pleiotropy
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
01:17Karyotyping
01:43Incomplete Dominance