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Title: Phenotypic spectrum of dynamin 2 mutations in Charcot-Marie-Tooth neuropathy
Authors: Claeys, Kristl ×
Züchner, Stephan
Kennerson, Marina
Berciano, José
Garcia, Antonio
Verhoeven, Kristien
Storey, Elsdon
Merory, John R
Bienfait, Henriette M E
Lammens, Martin
Nelis, Eva
Baets, Jonathan
De Vriendt, Els
Berneman, Zwi N
De Veuster, Ilse
Vance, Jefferey M
Nicholson, Garth
Timmerman, Vincent
De Jonghe, Peter #
Issue Date: Jul-2009
Publisher: Macmillan
Series Title: Brain vol:132 issue:Pt 7
Article number: 10.1093/brain/awp115
Abstract: Dominant intermediate Charcot-Marie-Tooth neuropathy type B is caused by mutations in dynamin 2. We studied the clinical, haematological, electrophysiological and sural nerve biopsy findings in 34 patients belonging to six unrelated dominant intermediate Charcot-Marie-Tooth neuropathy type B families in whom a dynamin 2 mutation had been identified: Gly358Arg (Spain); Asp551_Glu553del; Lys550fs (North America); Lys558del (Belgium); Lys558Glu (Australia, the Netherlands) and Thr855_Ile856del (Belgium). The Gly358Arg and Thr855_Ile856del mutations were novel, and in contrast to the other Charcot-Marie-Tooth-related mutations in dynamin 2, which are all located in the pleckstrin homology domain, they were situated in the middle domain and proline-rich domain of dynamin 2, respectively. We report the first disease-causing mutation in the proline-rich domain of dynamin 2. Patients with a dynamin 2 mutation presented with a classical Charcot-Marie-Tooth phenotype, which was mild to moderately severe since only 3% of the patients were wheelchair-bound. The mean age at onset was 16 years with a large variability ranging from 2 to 50 years. Interestingly, in the Australian and Belgian families, which carry two different mutations affecting the same amino acid (Lys558), Charcot-Marie-Tooth cosegregated with neutropaenia. In addition, early onset cataracts were observed in one of the Charcot-Marie-Tooth families. Our electrophysiological data indicate intermediate or axonal motor median nerve conduction velocities (NCV) ranging from 26 m/s to normal values in four families, and less pronounced reduction of motor median NCV (41-46 m/s) with normal amplitudes in two families. Sural nerve biopsy in a Dutch patient with Lys558Glu mutation showed diffuse loss of large myelinated fibres, presence of many clusters of regenerating myelinated axons and fibres with focal myelin thickenings--findings very similar to those previously reported in the Australian family. We conclude that dynamin 2 mutations should be screened in the autosomal dominant Charcot-Marie-Tooth neuropathy families with intermediate or axonal NCV, and in patients with a classical mild to moderately severe Charcot-Marie-Tooth phenotype, especially when Charcot-Marie-Tooth is associated with neutropaenia or cataracts.
URI: 
ISSN: 0006-8950
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Faculty of Medicine - miscellaneous
× corresponding author
# (joint) last author

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