Analyzing histopathological features of rare charcot-marie-tooth neuropathies to unravel their pathogenesis
| Autor: | Luigi M.E. Grimaldi, Elisabetta Munerati, Sara Benedetti, Maurizio Ferrari, Angelo Quattrini, Lara Piantoni, Maria Chiara Malaguti, Nilo Riva, Silvia Coviello, Marina Scarlato, Ivana Spiga, Federica Cerri, Maurizio De Pellegrin, Alessandra Bolino, Maria Giovanna Marrosu, Patrizia Dacci, Raffaella Fazio, Emanuela Di Pierri, Giancarlo Comi, Maria Grazia Natali Sora, Stefano C. Previtali |
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| Přispěvatelé: | Benedetti, S, Previtali, Sc, Coviello, S, Scarlato, M, Cerri, F, DI PIERRI, E, Piantoni, L, Spiga, I, Fazio, R, Riva, N, NATALI SORA, Mg, Dacci, P, Malaguti, Mc, Munerati, E, Grimaldi, Lm, Marrosu, Mg, DE PELLEGRIN, M, Ferrari, Maurizio, Comi, Giancarlo, Quattrini, A, Bolino, A. |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Pathology medicine.medical_specialty Adolescent DNA Mutational Analysis MFN2 HSP27 Heat-Shock Proteins Sural nerve medicine.disease_cause Connexins GTP Phosphohydrolases Central nervous system disease Pathogenesis Cohort Studies Mitochondrial Proteins Young Adult Degenerative disease Arts and Humanities (miscellaneous) Sural Nerve Charcot-Marie-Tooth Disease Biopsy medicine Humans Child Pathological Heat-Shock Proteins Aged Retrospective Studies Aged 80 and over Mutation medicine.diagnostic_test business.industry Intracellular Signaling Peptides and Proteins Membrane Proteins Middle Aged medicine.disease Phosphoproteins Ether-A-Go-Go Potassium Channels nervous system diseases Female Neurology (clinical) business Demyelinating Diseases Molecular Chaperones Transcription Factors |
| Zdroj: | Archives of neurology. 67(12) |
| ISSN: | 1538-3687 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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