Late-onset CMT2 associated with a novel missense mutation in the cytoplasmic domain of the MPZ gene

Phenotypic variations have been reported in Charcot-Marie-Tooth disease type 2 (CMT2) including age-at-onset, disease progression and severity. Sporadic cases with CMT2 have also been demonstrated by genetic test. We here report a patient with late-onset CMT2 without family history, who developed gait disturbance at the age of 68. Sequence analysis revealed a novel heterozygous Arg198Gly mutation in the cytoplasmic domain of the major peripheral myelin protein zero (MPZ). The mutation is located in the protein kinase C (PKC) alpha substrate motif (RSTK) of MPZ, presumably leading to the loss of PKC-mediated phosphorylation in adhesion. Routine genetic test for CMT is not recommended for every patient with late-onset peripheral neuropathy without known causes, however, the genetic test may be taken into consideration if the patient shows a clinical phenotype similar to that of CMT, and the possibility of a de novo mutation cannot be excluded.