The phenotype of the Gly94fsX222 PMP22 insertion

J Peripher Nerv Syst. 2011 Jun;16(2):113-8. doi: 10.1111/j.1529-8027.2011.00333.x.

Abstract

Point mutations in PMP22 are relatively rare and the phenotype may vary from mild hereditary neuropathy with liability to pressure palsies (HNPP) to severe Charcot-Marie-Tooth type 1 (CMT1). We describe the phenotype of the Gly94fsX222 mutation in the PMP22 gene. Medical records of all patients were reviewed and 11 patients were re-examined. EMG was carried out in nine patients and nerve biopsy in one. Thirteen patients originating from seven families with a Gly94fsX222 mutation were included and consisted of 10 women and 3 men with a median age of 41 years (range 7-67). Five index patients were originally suspected of CMT1. Ten patients had abnormal motor skills during childhood. Nine patients had a history of pressure palsies. Involvement of the olfactory, trigeminal, facial, and pudendal nerves occurred in three patients. Twelve patients had pes cavus and one scoliosis. Distal anterior leg and distal arm weakness were found in 12 and 4 patients, respectively. Twelve patients had distal leg sensory abnormalities. Electrophysiological examination revealed a demyelinating sensorimotor neuropathy, both resembling CMT1 and HNPP. Sural nerve biopsy showed demyelinating neuropathy with presence of tomacula. More than three-fourths of the patients with Gly94fsX222 mutation demonstrated a CMT1 phenotype combined with transient deficits. Clinicians should test for this mutation in those patients exhibiting a generalised neuropathy combined with compressive like episodes.

MeSH terms

  • Adolescent
  • Adult
  • Arthrogryposis / genetics*
  • Arthrogryposis / pathology
  • Arthrogryposis / physiopathology*
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / pathology
  • Charcot-Marie-Tooth Disease / physiopathology*
  • Child
  • Electrophysiology
  • Female
  • Hereditary Sensory and Motor Neuropathy / genetics*
  • Hereditary Sensory and Motor Neuropathy / pathology
  • Hereditary Sensory and Motor Neuropathy / physiopathology*
  • Humans
  • Male
  • Mutation, Missense
  • Myelin Proteins / genetics*
  • Phenotype
  • Point Mutation
  • Young Adult

Substances

  • Myelin Proteins
  • PMP22 protein, human

Supplementary concepts

  • Tomaculous neuropathy