Genetics of the Charcot-Marie-Tooth disease in the Spanish Gypsy population: the hereditary motor and sensory neuropathy-Russe in depth

Authors

  • T Sevilla,

    1. Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED), Valencia, Spain
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  • D Martínez-Rubio,

    1. Genetics and Molecular Medicine Unit, Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (CSIC), Valencia, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Valencia, Spain
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  • C Márquez,

    1. Department of Neurology, Hospital Virgen del Rocío, Seville, Spain
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  • C Paradas,

    1. Department of Neurology, Hospital Virgen del Rocío, Seville, Spain
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  • J Colomer,

    1. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Valencia, Spain
    2. Department of Neurology, Hospital Sant Joan de Déu, Barcelona, Spain
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  • T Jaijo,

    1. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Valencia, Spain
    2. Grupo de Investigación en Enfermedades Neurosensoriales, Instituto de Investigación Sanitaria (IIS) La Fe, Valencia, Spain
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  • JM Millán,

    1. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Valencia, Spain
    2. Grupo de Investigación en Enfermedades Neurosensoriales, Instituto de Investigación Sanitaria (IIS) La Fe, Valencia, Spain
    3. Genetics Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain
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  • F Palau,

    1. Genetics and Molecular Medicine Unit, Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (CSIC), Valencia, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Valencia, Spain
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  • C Espinós

    Corresponding author
    1. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Valencia, Spain
    2. Neurogenetics Platform, Instituto de Investigación Sanitaria (IIS) La Fe, Valencia, Spain
    3. Department of Genetics, University of Valencia, Valencia, Spain
    • Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain
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  • The authors declare no conflict of interest.

Corresponding author: Dr Carmen Espinós, Hospital Universitari i Politècnic La Fe, Plataforma de Neurogenética, Unit 755 CIBERER, Escuela de Enfermería, Sótano, Avd de Campanar, 20. 46009 Valencia, Spain.

Tel.: +34 96 1973324;

fax: +34 96 3696386;

e-mail: cespinos@ciberer.es

Abstract

Four private mutations responsible for three forms demyelinating of Charcot-Marie-Tooth (CMT) or hereditary motor and sensory neuropathy (HMSN) have been associated with the Gypsy population: the NDRG1 p.R148X in CMT type 4D (CMT4D/HMSN-Lom); p.C737_P738delinsX and p.R1109X mutations in the SH3TC2 gene (CMT4C); and a G>C change in a novel alternative untranslated exon in the HK1 gene causative of CMT4G (CMT4G/HMSN-Russe). Here we address the findings of a genetic study of 29 Gypsy Spanish families with autosomal recessive demyelinating CMT. The most frequent form is CMT4C (57.14%), followed by HMSN-Russe (25%) and HMSN-Lom (17.86%). The relevant frequency of HMSN-Russe has allowed us to investigate in depth the genetics and the associated clinical symptoms of this CMT form. HMSN-Russe probands share the same haplotype confirming that the HK1 g.9712G>C is a founder mutation, which arrived in Spain around the end of the 18th century. The clinical picture of HMSN-Russe is a progressive CMT disorder leading to severe weakness of the lower limbs and prominent distal sensory loss. Motor nerve conduction velocity was in the demyelinating or intermediate range.

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