Phenotypic variation of a novel nonsense mutation in the P0 intracellular domain

Mutations in the gene for the peripheral myelin protein zero (P0, MPZ) caus e type 1B of Charcot-Marie-Tooth sensorimotor neuropathy (CMT1B). Here we r eport a German family with a novel heterozygous P0 nonsense mutation (G206X ) that supposedly removes four-fifths of the amino acid residues constituti ng the P0 intracellular domain. The 12-year-old propositus had childhood-on set CMT1B associated with bilateral pes cavus, moderate lower limb weakness , and mildly reduced sensory qualities in the distal legs. The electrophysi ology was consistent with a demyelinating neuropathy. He inherited the muta tion from his mother who had no complaints but slight pes cavus deformity a nd slow nerve conduction velocities (NCV). Conclusively, truncating mutatio ns within the P0 intracellular domain do not necessarily cause a severe phe notype such as Dejerine-Sottas syndrome (DSS) or congenital hypomyelinating neuropathy (CHN), but can result in mild or moderate CMT1B with intrafamil ial clinical variability. (C) 2001 Elsevier Science B.V. All rights reserve d.