Highlights
- •Our data suggest that early onset CMT2A was not always with severe symptoms in our cohort.
- •Either above 38 m/s or unrecordable change in MNCV should be considered as common electrophysiological change of CMT2A.
- •Mixed axonal degeneration and demyelination in sural nerve was an interesting pathological change in our cases.
- •Exon 4 and the amino acid residue at position 94 of the Mitofsin 2 protein was the most frequent mutation seen in our cohort similar with other reports.
Abstract
Background
Charcot–Marie–Tooth 2A (CMT2A) is caused by mutations in mitochondrial fusion protein
mitofusin 2 (MFN2). CMT2A had a large variety of clinical symptoms and several cohort studies were
published recently. This study is to summarized the clinical, electrophysiological,
pathological and genetic features in Han Chinese CMT2A.
Methods
20 patients from 12 unrelated Chinese families with MFN2 related CMT2A were collected. Clinical symptom, nerve conduction velocity study,
sural nerve pathology and MFN2 gene mutation were retrospectively analyzed.
Results
We confirmed MFN2 gene mutation in 12 indexes. Nineteen of 20 (95%) patients were classified as early
onset phenotypes of CMT2A, including four cases (20%) with infantile onset. Motor
nerve conduction velocity (MNCV) of median nerve was above 38 m/s in 50% of patients and not recordable in remaining patients. MNCV was not affected
by onset age, disease course and mutation site in different patients and MNCV had
no correlation with severity of symptoms. Sural nerve biopsy revealed mixed axonal
and demyelination change. Loss of myelinated fibers and atypical onions was found
in all cases. Electron microscopic (EM) examination of sural nerve confirmed mitochondrial
vacuation and aggregation both in myelinated and unmyelinated axons. Eight mutations
were detected in 12 indexes, including two novel mutations. The amino acid residue
at position 94 of MFN2 protein was a hot spot in Han Chinese patients, followed by R104W.
Conclusions
Eraly onset, even infantile onset was more common in our Chinese population. MNCV
of median nerve could be either above 38 m/s or unrecordable in CMT2A. Pathologically, mixed axon and myelin change should
be considered since onion change was frequently observed in most CMT2A.
Keywords
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Article info
Publication history
Published online: August 26, 2015
Accepted:
August 19,
2015
Received in revised form:
July 18,
2015
Received:
May 9,
2015
Identification
Copyright
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
