Mutations in the Dynamin 2 gene (DNM2) cause autosomal dominant centronuclear 
myopathy or autosomal dominant (AD) Charcot-Marie-Tooth (CMT) disease. Here the 
authors report one large Czech family with 15 members affected with an AD CMT 
phenotype of extraordinary variability. Genetic linkage analysis using SNP 
arrays revealed a locus of about 9.6 Mb on chromosome 19p13.1-13.2. In this 
critical interval, 373 genes were located. The only gene herein known to be 
associated with an intermediate type of CMT was Dynamin 2 (DNM2). Subsequent 
sequence analysis of the DNM2 gene in the index patient revealed a novel 
missense mutation p.Met580Thr. This missense mutation segregated with the 
neuropathy, indicating the causal character of this mutation. The phenotype of 
CMT in this family shows mild to moderate impairment with relatively preserved 
upper limbs and a very broad range of the onset of clinical symptoms from an 
early onset around the age of 12 to the late onset during the fifth decade. 
Electrophysiology showed an intermediate type of peripheral neuropathy. The 
motor median nerve conduction velocity varied from 36 m/s to normal values with 
signs of asymmetrical affection of peripheral nerves. No additional symptoms 
such as cranial nerve involvement, cataract, and signs of neutropenia or 
myopathy syndrome were observed in any member of the family yet. The progression 
was slow with no loss of ambulation. The authors suggest that the 
characterization of clinical variability in a single family may help to direct 
the genetic analysis directly to the rarely observed DNM2 mutations.