title: Late-onset CMT2 associated with a novel missense mutation in the cytoplasmic domain of the MPZ gene.
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.
authors.affiliation: Department of Neurology, Hyogo Brain and Heart Centre, Saisho-Ko 520, Himeji City 670-0981, Hyogo Prefecture, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Shimizu
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Oka
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Kawarai
authors.forename: Koichiro
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Saji
authors.forename: Makoto
authors.initials: M
authors.lastname: Tadano
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Antonio
authors.initials: A
authors.lastname: Orlacchio
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kita
mesh_terms: D000368:Aged; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism*; D004576:Electromyography; D055724:Electrophysiological Phenomena; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D006801:Humans; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D018908:Muscle Weakness / Q000209:etiology; D020125:Mutation, Missense / Q000235:genetics*; D018993:Myelin P0 Protein / Q000235:genetics*; D009431:Neural Conduction / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D013497:Sural Nerve / Q000473:pathology
chemical_list: D018993:Myelin P0 Protein; D011493:Protein Kinase C