Analyzing histopathological features of rare Charcot-Marie-Tooth neuropathies to unravel their pathogenesis

Sara Benedetti, Stefano Carlo Previtali, Silvia Coviello, Marina Scarlato, Federica Cerri, Emanuela Di Pierri, Lara Piantoni, Ivana Spiga, Raffaella Fazio, Nilo Riva, Maria Grazia Natali Sora, Patrizia Dacci, Maria Chiara Malaguti, Elisabetta Munerati, Luigi Maria Edoardo Grimaldi, Maria Giovanna Marrosu, Maurizio De Pellegrin, Maurizio Ferrari, Giancarlo Comi, Angelo QuattriniAlessandra Bolino

Research output: Contribution to journalArticlepeer-review


Background: Charcot-Marie-Tooth (CMT) neuropathies are very heterogeneous disorders from both a clinical and genetic point of view. The CMT genes identified so far encode different proteins that are variably involved in regulating Schwann cells and/or axonal functions. However, the function of most of these proteins still remains to be elucidated. Objective: To characterize a large cohort of patients with demyelinating, axonal, and intermediate forms of CMT neuropathy. Design: A cohort of 131 unrelated patients were screened for mutations in 12 genes responsible for CMT neuropathies. Demyelinating, axonal, and intermediate forms of CMT neuropathy were initially distinguished as usual on the basis of electrophysiological criteria and clinical evaluation. A sural nerve biopsy was also performed for selected cases. Accordingly, patients underwent first-level analysis of the genes most frequently mutated in each clinical form of CMT neuropathy. Results: Although our cohort had a particularly high percentage of cases of rare axonal and intermediate CMT neuropathies, we found mutations in 40% of patients. Among identified changes, 7 represented new mutations occurring in the MPZ, GJB1, EGR2, MFN2, NEFL, and HSBP1/HSP27 genes. Histopathological analysis performed in selected cases revealed morphological features, which correlated with the molecular diagnosis and provided evidence of the underlying pathogenetic mechanism. Conclusion: Clinical and pathological analysis of patients with CMT neuropathies contributes to our understanding of the molecular mechanisms of CMT neuropathies.

Original languageEnglish
Pages (from-to)1498-1505
Number of pages8
JournalArchives of Neurology
Issue number12
Publication statusPublished - Dec 2010

ASJC Scopus subject areas

  • Clinical Neurology


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