Late-onset CMT2 associated with a novel missense mutation in the cytoplasmic dom

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Clin Neurol Neurosurg. 2010 Aug 25

Late-onset CMT2 associated with a novel missense mutation in the cytoplasmic

domain of the MPZ gene.

Shimizu H, Oka N, Kawarai T, Taniguchi K, Saji N, Tadano M, Bernardi G,

Orlacchio A, Kita Y.

Department of Neurology, Hyogo Brain and Heart Centre, Saisho-Ko 520, Himeji

City 670-0981, Hyogo Prefecture, Japan.

Abstract

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.