title: Phenotypic variation of a novel nonsense mutation in the P0 intracellular domain.
abstract: Mutations in the gene for the peripheral myelin protein zero (P0, MPZ) cause type 1B of Charcot-Marie-Tooth sensorimotor neuropathy (CMT1B). Here we report a German family with a novel heterozygous P0 nonsense mutation (G206X) that supposedly removes four-fifths of the amino acid residues constituting the P0 intracellular domain. The 12-year-old propositus had childhood-onset CMT1B associated with bilateral pes cavus, moderate lower limb weakness, and mildly reduced sensory qualities in the distal legs. The electrophysiology was consistent with a demyelinating neuropathy. He inherited the mutation from his mother who had no complaints but slight pes cavus deformity and slow nerve conduction velocities (NCV). Conclusively, truncating mutations within the P0 intracellular domain do not necessarily cause a severe phenotype such as Dejerine-Sottas syndrome (DSS) or congenital hypomyelinating neuropathy (CHN), but can result in mild or moderate CMT1B with intrafamilial clinical variability.
authors.affiliation: Institut für Neuropathologie, Klinikum der Rheinisch-Westfälischen Technischen Hochschule, Pauwelsstrasse 30, D-52974 Aachen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Senderek
authors.forename: V T
authors.initials: VT
authors.lastname: Ramaekers
authors.forename: K
authors.initials: K
authors.lastname: Zerres
authors.forename: S
authors.initials: S
authors.lastname: Rudnik-Schöneborn
authors.forename: J M
authors.initials: JM
authors.lastname: Schröder
authors.forename: C
authors.initials: C
authors.lastname: Bergmann
mesh_terms: D000328:Adult; D000368:Aged; D002490:Central Nervous System / Q000503:physiopathology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D005858:Germany; D006801:Humans; D008297:Male; D018993:Myelin P0 Protein / Q000235:genetics*; D010641:Phenotype; D017434:Protein Structure, Tertiary / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D018993:Myelin P0 Protein