Related Experiment Video
Updated: Jun 7, 2025
07:43
Modeling Charcot-Marie-Tooth Disease In Vitro by Transfecting Mouse Primary Motoneurons
Published on: January 7, 2019
6.9K
Phenotype-genotype correlation in X-linked Charcot-Marie-Tooth disease: A French cohort study
Luce Barbat du Closel1, Nathalie Bonello-Palot2, Emilien Delmont1
1Reference Center for Neuromuscular Disorders and ALS, APHM, CHU La Timone, Filnemus, ERN Neuro-NMD, Marseille, France.
European Journal of Neurology
|November 21, 2024
Summary
Genetic variants in transmembrane domains of X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) are linked to more severe neuropathy. Understanding these genotype-phenotype correlations is crucial for future clinical trials in CMTX1 patients.
Area of Science:
- Neurology
- Genetics
- Hereditary Neuropathies
Background:
- X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is a common inherited neuropathy with no cure.
- Preclinical research suggests potential for future clinical trials.
Purpose of the Study:
- To investigate genotype-phenotype correlations in CMTX1.
- To aid in forming balanced patient groups for upcoming clinical trials.
Main Methods:
- Retrospective analysis of 275 CMTX1 patients from 13 French reference centers.
- Systematic data collection on genetics, clinical presentation, and nerve conduction studies.
Main Results:
- 87 distinct variants were identified across 162 families.
- Variants in transmembrane domains correlated with increased disease severity (CMT-ES 10.5 vs. 7.1-8.7).
- Transmembrane domain variants showed earlier onset, slower nerve conduction, and greater motor amplitude loss.
Conclusions:
- A significant correlation exists between the mutated protein domain and clinical phenotype in CMTX1.
- Variants in transmembrane domains predict a more severe clinical and electrophysiological profile.
- Genotype may serve as a prognostic indicator for CMTX1, essential for clinical trial stratification.
Related Concept Videos
01:35Pedigree Analysis
84.0K
Overview
84.0K
01:43Incomplete Dominance
21.6K
Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
21.6K
01:33Pleiotropy
39.8K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
39.8K
01:19X-linked Traits
53.6K
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
53.6K
01:11Genetic Lingo
101.1K
Overview
101.1K
01:43Sex-linked Disorders
100.5K
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
100.5K