LETTER TO JMG

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

R Claramunt¹, L Pedrola¹, T Sevilla², A López de Munain³, J Berciano⁴, A Cuesta¹, B Sánchez-Navarro¹, J M Millán⁵, G M Saifi⁶, J R Lupski⁶, J J Vílchez², C Espinós¹, F Palau¹

¹ Laboratory of Genetics and Molecular Medicine, Department of Genomics and Proteomics, Instituto de Biomedicina, CSIC, Valencia, Spain
² Department of Neurology, Hospital Universitari La Fe, Valencia, Spain
³ Department of Neurology, Hospital Donostia, San Sebastian, Spain
⁴ Department of Neurology, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain
⁵ Genetics Unit, Hospital Universitari La Fe, Valencia, Spain
⁶ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

Correspondence to:
Correspondence to:
Dr Francesc Palau
Department of Genomics and Proteomics, Instituto de Biomedicina, CSIC, C/Jaume Roig 11, 46010 Valencia, Spain; fpalau@ibv.csic.es

Received 28 April 2004
Revised version received 23 June 2004

Abbreviations: CHN, congenital hypomyelinating neuropathy; CMAP, compound motor action potential; CMT disease, Charcot-Marie-Tooth disease; DSN, Déjérine-Sottas neuropathy; NCVs, nerve conduction velocities; SNAP, sensory nerve action potential

Keywords: Charcot-Marie-Tooth disease type 4A; founder effect; GDAP1 gene; Mendelian inheritance variability

The first 150 words of the full text of this article appear below.

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. . . [Full text of this article]

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