title: [Guidelines for molecular diagnosis of Charcot-Marie-Tooth disease].
abstract: BACKGROUND
  Charcot-Marie-Tooth disease (CMT) is the most frequent form of inherited neuropathy. In accordance with the inheritance pattern and degree of slowing of motor conduction velocity (MCV) of the median nerve, CMT encompasses five main forms: CMT1 (autosomal dominant [AD] or X-linked transmission and MCV < 38 m/s); CMT2 (AD or X-linked transmission and MCV > 38 m/s); CMT4 (autosomal recessive [AR] and severe slowing of MCV); AR-CMT2 (AR transmission and MCV > 38 m/s); and DI-CMT (intermediate form with AD transmission and MCV between 30 and 40 m/s). In spite of its stereotyped semiological repertoire (basically, symptoms and signs of sensory-motor polyneuropathy and pes cavus), CMT seems to be one of the most complex hereditary neurodegenerative syndromes, 31 causative genes having been cloned.
  
  
  METHODS
  This paper is aimed at performing a nosological review of the disease, emphasising the guidelines for its molecular diagnosis. Genetic epidemiological studies and genotypes reported in Spanish patients are revised.
  
  
  CONCLUSIONS
  In the great majority of CMT cases, mutations involve a reduced number of genes, namely: for CMT1, PMP22, GJB1 and MPZ; for CMT2, MFN2 and GJB1; for CMT4, GDAP1, and NDRG1, HK1 and SH3TC2 (gypsies); for AR-CMT2, GDAP1; and for DI-CMT, GJB1 and MPZ. Given their low prevalence, mutations in other pathogenic genes should be investigated after discarding the previous ones. There is no place for the indiscriminate use of diagnostic CMT genetic panels.
authors.affiliation: Servicio de Neurología, Hospital Universitario Marqués de Valdecilla (IFIMAV), Universidad de Cantabria, CIBERNED, Santander, España. jaberciano@humv.es
authors.forename: J
authors.initials: J
authors.lastname: Berciano
authors.forename: T
authors.initials: T
authors.lastname: Sevilla
authors.forename: C
authors.initials: C
authors.lastname: Casasnovas
authors.forename: R
authors.initials: R
authors.lastname: Sivera
authors.forename: J J
authors.initials: JJ
authors.lastname: Vílchez
authors.forename: J
authors.initials: J
authors.lastname: Infante
authors.forename: C
authors.initials: C
authors.lastname: Ramón
authors.forename: A L
authors.initials: AL
authors.lastname: Pelayo-Negro
authors.forename: I
authors.initials: I
authors.lastname: Illa
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis* / Q000235:genetics*; D005819:Genetic Markers; D017408:Guidelines as Topic; D006801:Humans; D017720:Molecular Epidemiology; D009154:Mutation / Q000235:genetics / Q000502:physiology
chemical_list: D005819:Genetic Markers