Guidelines for molecular diagnosis of Charcot-Marie-Tooth disease
Por:
Berciano, J, Sevilla, T, Casasnovas, C, Sivera, R, Vilchez, JJ, Infante, J, Ramon, C, Pelayo-Negro, AL, Illa, I
Publicada:
1 abr 2012
Resumen:
Introduction: 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.
Development: 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. (C) 2011 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L. All rights reserved.
Filiaciones:
Berciano, J:
Univ Cantabria, Serv Neurol, Hosp Univ Marques de Valdecilla IFIMAV, CIBERNED, E-39005 Santander, Spain
Sevilla, T:
Hosp Univ Fe, Serv Neurol, CIBERNED, Valencia, Spain
Casasnovas, C:
Ctr Diagnost Genet & Mol Malalties Hereditaries, Inst Invest Biomed Bellvitge IDIBELL, Serv Neurol, Barcelona, Spain
Sivera, R:
Hosp Univ Fe, Serv Neurol, CIBERNED, Valencia, Spain
Vilchez, JJ:
Hosp Univ Fe, Serv Neurol, CIBERNED, Valencia, Spain
Infante, J:
Univ Cantabria, Serv Neurol, Hosp Univ Marques de Valdecilla IFIMAV, CIBERNED, E-39005 Santander, Spain
Ramon, C:
Hosp Univ Cent Asturias, Serv Neurol, Oviedo, Spain
Pelayo-Negro, AL:
Univ Cantabria, Serv Neurol, Hosp Univ Marques de Valdecilla IFIMAV, CIBERNED, E-39005 Santander, Spain
Illa, I:
Hosp Santa Creu i St Pau, Serv Neurol, CIBERNED, Barcelona, Spain
Open Access
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