title: Severe phenotype with cis-acting heterozygous PMP22 mutations.
abstract: We report on a 20-year-old male with severe Charcot-Marie-Tooth (CMT) disease and a de novo deletion (c.281delG, p.G94AfsX17) on the paternal PMP22 allele harboring c.353C>T (p.T118M). RNA-based sequence analysis confirmed the absence of nonsense-mediated decay and the presence of the mutant transcripts in Epstein-Barr virus-transformed lymphoblastoid cells of our patient. His clinical findings included early onset of polyneuropathy, loss of muscle mass with distal pareses, hammer toes, and progressive scoliosis. There was no neuropsychological alteration. Our results suggest that the deletion c.281delG alone is responsible for the severe CMT phenotype. To the best of our knowledge, this is the second report on a proven paternal origin of a de novo single-base mutation in the PMP22 gene.
authors.affiliation: Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland. niedrist@medgen.uzh.ch
authors.forename: D
authors.initials: D
authors.lastname: Niedrist
authors.forename: F
authors.initials: F
authors.lastname: Joncourt
authors.forename: G
authors.initials: G
authors.lastname: Mátyás
authors.forename: A
authors.initials: A
authors.lastname: Müller
mesh_terms: D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009185:Myelin Proteins / Q000235:genetics*; D010641:Phenotype
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human