title: Focally folded myelin in Charcot-Marie-Tooth neuropathy type 1B with Ser49Leu in the myelin protein zero.
abstract: Charcot-Marie-Tooth disease type 1 B (CMT1B) is a demyelinating neuropathy caused by mutations in the myelin protein zero (P0) gene (MPZ). A few cases of CMT1B were recently found to be characterized by focally folded myelin sheaths in nerve biopsy specimens; the significance of this association is unknown. Here, we describe two unrelated pedigrees harboring a heterozygous Ser49Leu substitution in P0ex. In both pedigrees, the mutation caused a late-onset, relatively mild CMT1B; in one pedigree, two patients had atrophy of peroneal muscles but hypertrophy of the gastrocnemius muscles. The sural nerve biopsy performed in the two index cases revealed an identical chronic demyelinating and remyelinating neuropathy dominated by focal foldings of the myelin sheath shaped either as tomacula or as out/infoldings. The report adds Ser49Leu to the mutations of P0ex associated with focally folded myelin and provides strong evidence that such a structural alteration of the myelin sheath reflects a distinct pathogenetic mechanism in a subgroup of CMT1B.
authors.affiliation: Department of Neurological and Visual Sciences, University of Verona, Policlinico Giambattista Rossi, Italy.
authors.forename: G M
authors.initials: GM
authors.lastname: Fabrizi
authors.forename: F
authors.initials: F
authors.lastname: Taioli
authors.forename: T
authors.initials: T
authors.lastname: Cavallaro
authors.forename: F
authors.initials: F
authors.lastname: Rigatelli
authors.forename: A
authors.initials: A
authors.lastname: Simonati
authors.forename: G
authors.initials: G
authors.lastname: Mariani
authors.forename: P
authors.initials: P
authors.lastname: Perrone
authors.forename: N
authors.initials: N
authors.lastname: Rizzuto
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D006984:Hypertrophy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D007930:Leucine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000502:physiology; D018993:Myelin P0 Protein / Q000235:genetics* / Q000378:metabolism; D009186:Myelin Sheath / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D010375:Pedigree; D012694:Serine / Q000235:genetics*; D013497:Sural Nerve / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D018993:Myelin P0 Protein; D012694:Serine; D007930:Leucine