title: T118M PMP22 mutation causes partial loss of function and HNPP-like neuropathy.
abstract: OBJECTIVE
  To determine the clinical consequences of the PMP22 point mutation, T118M, which has been previously considered to either cause an autosomal recessive form of Charcot-Marie-Tooth (CMT) disease or be a benign polymorphism.
  
  
  METHODS
  We analyzed patients from five separate kindreds and characterized their peripheral nerve function by clinical and electrophysiological methods.
  
  
  RESULTS
  All heterozygous patients had clinical and/or electrophysiological features of a neuropathy similar to hereditary neuropathy with liability to pressure palsies (HNPPs). The homozygous patient had a severe axonal neuropathy without features of demyelination.
  
  
  CONCLUSIONS
  These findings suggest that T118M PMP22 retains some normal PMP22 activity, allowing the formation of compact myelin and normal nerve conduction velocities in the homozygous state. Taken together, these findings suggest that T118M is a pathogenic mutation causing a dominantly inherited form of CMT by a partial loss of PMP22 function.
authors.affiliation: Department of Neurology and Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA. m.shy@wayne.edu
authors.forename: Michael E
authors.initials: ME
authors.lastname: Shy
authors.forename: Mena T
authors.initials: MT
authors.lastname: Scavina
authors.forename: Alisa
authors.initials: A
authors.lastname: Clark
authors.forename: Karen M
authors.initials: KM
authors.lastname: Krajewski
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: John
authors.initials: J
authors.lastname: Kamholz
authors.forename: Edwin
authors.initials: E
authors.lastname: Kolodny
authors.forename: Kinga
authors.initials: K
authors.lastname: Szigeti
authors.forename: Richard A
authors.initials: RA
authors.lastname: Fischer
authors.forename: Gulam Mustafa
authors.initials: GM
authors.lastname: Saifi
authors.forename: Steven S
authors.initials: SS
authors.lastname: Scherer
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009185:Myelin Proteins / Q000235:genetics*; D009431:Neural Conduction / Q000502:physiology; D010525:Peripheral Nerves / Q000503:physiopathology; D010641:Phenotype; D013912:Threonine / Q000235:genetics*
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human; D013912:Threonine; D008715:Methionine