title: Parental mosaicism of a novel PMP22 mutation with a minimal neuropathic phenotype.
abstract: Genetic germinal and somatic mosaicisms of dominant Charcot-Marie-Tooth disease (CMT) mutations are rarely reported and/or recognized. We describe a novel heterozygous p.Trp39Cys missense mutation in the extracellular domain of the peripheral myelin protein 22 (PMP22) associated with an early-onset demyelinating CMT type 1 E (CMT1E) in two siblings born from asymptomatic non-consanguineous parents. The 29-year-old mother, harboring approximately 20% of the mutant PMP22 allele in blood, had minor signs of distal polyneuropathy (pes cavus, decreased ankle jerk reflexes and vibration sense in legs) and slight reduction of sural nerve action potentials (SNAPs). Authors suggest that mutations of CMT-related genes which originate in post-zygotic stages may be associated with mild phenotypes of peripheral neuropathy.
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Movement Sciences, Section of Neuropathology, University of Verona, Verona, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Taioli
authors.forename: Laura
authors.initials: L
authors.lastname: Bertolasi
authors.forename: Domenico
authors.initials: D
authors.lastname: Ajena
authors.forename: Moreno
authors.initials: M
authors.lastname: Ferrarini
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cabrini
authors.forename: Alberto
authors.initials: A
authors.lastname: Crestanello
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Fabrizi
mesh_terms: D019943:Amino Acid Substitution; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000209:etiology / Q000235:genetics; D004568:Electrodiagnosis; D005091:Exons / Q000235:genetics; D006801:Humans; D008297:Male; D009030:Mosaicism; D020125:Mutation, Missense / Q000235:genetics / Q000502:physiology; D009185:Myelin Proteins / Q000235:genetics*; D009460:Neurologic Examination; D010375:Pedigree; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human