Abstract
We report a detailed study of eight patients from four Italian families presenting with autosomal recessive axonal Charcot-Marie-Tooth disease (AR-CMT2), characterized by early-onset and progressive severe weakness of all limbs. Vocal cord paresis was present in two cases. Sural nerve biopsy performed in three patients showed a severe neuropathy characterized by a predominant axonal involvement. Five novel mutations (p.Gln99stop, p.Gln122Lys, p.Arg125stop, p.Val219Asp, p.Asn297Lys) and one previously reported mutation (p.Leu239Phe) were identified in GDAP1 gene. GDAP1 mutations should be considered both in recessive and sporadic cases of early-onset axonal CMT.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Age Factors
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Age of Onset
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Amino Acid Substitution / genetics
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Axons / metabolism*
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Axons / pathology
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Charcot-Marie-Tooth Disease / genetics*
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Charcot-Marie-Tooth Disease / metabolism*
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Charcot-Marie-Tooth Disease / physiopathology
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Child
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Child, Preschool
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DNA Mutational Analysis
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Disease Progression
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Extremities / innervation
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Extremities / physiopathology
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Female
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Genes, Recessive / genetics
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Genetic Markers / genetics
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Genetic Testing
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Genotype
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Humans
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Infant
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Male
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Muscle Weakness / genetics
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Muscle Weakness / metabolism
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Muscle Weakness / physiopathology
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Mutation / genetics*
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism
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Peripheral Nerves / metabolism*
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Peripheral Nerves / pathology
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Peripheral Nerves / physiopathology
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Vocal Cord Paralysis / genetics
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Vocal Cord Paralysis / metabolism
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Vocal Cord Paralysis / physiopathology
Substances
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GDAP protein
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Genetic Markers
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Nerve Tissue Proteins