Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease

2005 ◽  
Vol 37 (3) ◽  
pp. 289-294 ◽  
Author(s):  
Stephan Züchner ◽  
Maher Noureddine ◽  
Marina Kennerson ◽  
Kristien Verhoeven ◽  
Kristl Claeys ◽  
...  
Keyword(s):  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Dynamin 2 ◽  
Tooth Disease

Mutations in the Pleckstrin Homology Domain of Dynamin 2 Cause Dominant Intermediate Charcot-Marie-Tooth Disease: LBS.002

Neurology ◽  
2005 ◽  
Vol 64 (10) ◽  
pp. 1826-1826 ◽  
Author(s):  
S. Zuchner ◽  
M. Noureddine ◽  
M. Kennerson ◽  
K. Verhoeven ◽  
K. Claeys ◽  
...  
Keyword(s):  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Dynamin 2 ◽  
Tooth Disease

scholarly journals A mutation associated with Charcot-Marie-Tooth disease enhances the formation of stable dynamin 2 complexes in cells

2021 ◽  
Author(s):  
Per Niklas Hedde ◽  
Barbara Barylko ◽  
Chi-Li Chiu ◽  
Joseph P Albanesi ◽  
David M Jameson ◽  
...  
Keyword(s):  
Self Assembly ◽  
Deletion Mutant ◽  
Intramolecular Interactions ◽  
Pleckstrin Homology Domain ◽  
Cytoplasmic Inclusions ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Close Proximity ◽  
Gtpase Activation ◽  
Dynamin 2

Mutations in dynamin 2 (DNM2) have been associated with two distinct motor disorders, Charcot-Marie-Tooth neuropathies (CMT) and centronuclear myopathy (CNM). The majority of these mutations are clustered in the pleckstrin homology domain (PHD) which engage in intramolecular interactions that suppress dynamin self-assembly and GTPase activation. CNM mutations in the PHD interferes with these intramolecular interactions, thereby blocking the formation of the auto-inhibited state. CMT mutations are located primarily on the opposite surface of the PHD, which is specialized for lipid PIP2 binding. It has been speculated that the distinct locations and interactions of residues mutated in CMT and CNM explain why each set of mutations cause either one disease or the other, despite their close proximity within the PHD sequence. We show that at least one CMT-causing mutant, lacking residues 555DEE557 (∆DEE), displays this inability to undergo auto-inhibition as observed in CNM-linked mutants. This ∆DEE deletion mutant induces the formation of abnormally large cytoplasmic inclusions similar to those observed for CNM-linked mutant R369W. We also found substantially reduced migration from the membrane of the ∆DEE deletion mutant. These findings call into question the molecular mechanism currently believed to underlie the absence of pathogenic overlap between DNM2-dependent CMT and CNM.

G.O. 9 Dynamin 2 mutations are associated with dominant intermediate Charcot-Marie-Tooth disease and dominant centronuclear myopathy

2006 ◽  
Vol 16 (9-10) ◽  
pp. 725
Author(s):  
K.G. Claeys ◽  
S. Züchner ◽  
M. Kennerson ◽  
K. Verhoeven ◽  
C. Ceuterick ◽  
...  
Keyword(s):  
Centronuclear Myopathy ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Dynamin 2 ◽  
Tooth Disease

Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease

Neurology ◽  
2007 ◽  
Vol 69 (3) ◽  
pp. 291-295 ◽  
Author(s):  
G. M. Fabrizi ◽  
M. Ferrarini ◽  
T. Cavallaro ◽  
I. Cabrini ◽  
R. Cerini ◽  
...  
Keyword(s):  
Novel Mutations ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Dynamin 2 ◽  
Tooth Disease
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