Genetics of Charcot-Marie-Tooth disease type 4A: mutations, inheritance, phenotypic variability, and founder effect

2005/04/01 by Reyes Claramunt, L Pedrola, T Sevilla +10 · 147 citations
Neuroscience · Medicine · #Hereditary Neurological Disorders #Botulinum Toxin and Related Neurological Disorders #Pes cavus #Hereditary motor and sensory neuropathy #Medicine #Nerve biopsy #Weakness #Sensory loss #Hypotonia #Hyporeflexia #Genetic heterogeneity #Peripheral neuropathy #Pathology #Disease #Anatomy #Genetics #Biology #Pediatrics #Phenotype #Surgery #Gene #Endocrinology

paper · pdf · doi:10.1136/jmg.2004.022178

published in Journal of Medical Genetics 42(4), 358-365 (BMJ)

openalex publication_date 2005/04/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/08

Abstract

Charcot-Marie-Tooth (CMT) disease is a motor and sensory neuropathy with clinical and genetic heterogeneity. Patients usually present in the first or second decade of life with distal muscle atrophy in the legs, areflexia, foot deformity (mainly pes cavus), and steppage gait. In most cases, hands are also involved as the disease progresses. CMT is the most frequent inherited neuropathy, with a prevalence in Spain of 28 in 100 000.1 Based on electrophysiological studies and histopathologic findings in nerve biopsies, CMT has been subcategorised into two main and distinct neuropathies: (i) demyelinating CMT (CMT1, MIM 118200) associated with reduction in a nerve conduction velocities (NCVs) in all nerves and segmental demyelination and remyelination ("onion bulbs"); and (ii) axonal CMT (CMT2, MIM 118220) associated with normal or almost normal NCVs and loss of myelinated axons. Other phenotypes are associated with motor and sensory nerve involvement: Déjérine-Sottas neuropathy (DSN, MIM 145900) is a severe demyelinating neuropathy with onset in infancy, delayed motor milestones, and NCVs less than 10 m/s; congenital hypomyelinating neuropathy (CHN, MIM 605253) is a dysmyelinating neuropathy characterised by infantile hypotonia, distal muscle weakness, and marked reduction of NCVs; hereditary neuropathy with liability to pressure palsies (HNPP, MIM 162500) is a milder sensory and motor neuropathy with periodic episodes of numbness, muscular weakness, and atrophy

Citations

• Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21
• Vocal cord and diaphragm paralysis, as clinical features of a French family with autosomal recessive Charot-Marie-Tooth disease, associated with a new mutation in the GDAP1 gene
• The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease
• Identification of novel GDAP1 mutations causing autosomal recessive Charcot-Marie-Tooth disease
• Variability of disease progression in a family with autosomal recessive CMT associated with a S194X and new R310Q mutation in the GDAP1 gene
• Evolutionary and Structural Analyses of GDAP1, Involved in Charcot-Marie-Tooth Disease, Characterize a Novel Class of Glutathione Transferase-Related Genes
• CMT4A: Identification of a Hispanic GDAP1 founder mutation
• Mutations in the ganglioside-induced differentiation-associated protein-1 (GDAP1) gene in intermediate type autosomal recessive Charcot-Marie-Tooth neuropathy
• Phenotypical Features of a Moroccan Family With Autosomal Recessive Charcot-Marie-Tooth Disease Associated With the S194X Mutation in the GDAP1 Gene

Cited by

• GDAP1 [wikipedia]