Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous 
group of peripheral neuropathies. Different chromosomal loci have been linked 
with three autosomal dominant, 'intermediate' types of CMT: DI-CMTA, DI-CMTB and 
DI-CMTC. We refined the locus associated with DI-CMTB on chromosome 19p12-13.2 
to 4.2 Mb in three unrelated families with CMT originating from Australia, 
Belgium and North America. After screening candidate genes, we identified unique 
mutations in dynamin 2 (DNM2) in all families. DNM2 belongs to the family of 
large GTPases and is part of the cellular fusion-fission apparatus. In 
transiently transfected cell lines, mutations of DNM2 substantially diminish 
binding of DNM2 to membranes by altering the conformation of the beta3/beta4 
loop of the pleckstrin homology domain. Additionally, in the Australian and 
Belgian pedigrees, which carry two different mutations affecting the same amino 
acid, Lys558, CMT cosegregated with neutropenia, which has not previously been 
associated with CMT neuropathies.