Analyzing Histopathological Features of Rare Charcot-Marie-Tooth Neuropathies to Unravel Their Pathogenesis

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

来源：Archives of Neurology, 2010, 67(12): 1498-1505.

DOI：10.1001/archneurol.2010.303

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.

• 出版日期2010-12