title: Four novel cases of periaxin-related neuropathy and review of the literature.
abstract: OBJECTIVE
  To report 4 cases of autosomal recessive hereditary neuropathy associated with novel mutations in the periaxin gene (PRX) with a review of the literature. Periaxin protein is required for the maintenance of peripheral nerve myelin. Patients with PRX mutations have early-onset autosomal recessive demyelinating Charcot-Marie-Tooth disease (CMT4F) or Déjèrine-Sottas neuropathy (DSN). Only 12 different mutations have been described thus far.
  
  
  METHODS
  Case reports and literature review.
  
  
  RESULTS
  Four patients from 3 unrelated families (2 siblings and 2 unrelated patients) were affected by an early-onset, slowly progressive demyelinating neuropathy with relevant sensory involvement. All carried novel frameshift or nonsense mutations in the PRX gene. The 2 siblings were compound heterozygotes for 2 PRX null mutations (p.Q547X and p.K808SfsX2), the third patient harbored a homozygous nonsense mutation (p.E682X), and the last patient had a homozygous 2-nt insertion predicting a premature protein truncation (p.S259PfsX55). Electrophysiologic analysis showed a severe slowing of motor nerve conduction velocities (MNCVs, between 3 and 15.3 m/s) with undetectable sensory nerve action potentials (SNAPs). Sural nerve biopsy, performed in 2 patients, demonstrated a severe demyelinating neuropathy and onion bulb formations. Interestingly, we observed some variability of disease severity within the same family.
  
  
  CONCLUSIONS
  These cases and review of the literature indicate that PRX-related neuropathies have early onset but overall slow progression. Typical features are prominent sensory involvement, often with sensory ataxia; a moderate-to-dramatic reduction of MNCVs and almost invariable absence of SNAPs; and pathologic demyelination with classic onion bulbs, and less commonly myelin folding and basal lamina onion bulbs.
authors.affiliation: Unit of Clinic of Central and Peripheral Degenerative Neuropathies, Carlo Besta Neurological Institute IRCCS Foundation, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Marchesi
authors.forename: M
authors.initials: M
authors.lastname: Milani
authors.forename: M
authors.initials: M
authors.lastname: Morbin
authors.forename: M
authors.initials: M
authors.lastname: Cesani
authors.forename: G
authors.initials: G
authors.lastname: Lauria
authors.forename: V
authors.initials: V
authors.lastname: Scaioli
authors.forename: G
authors.initials: G
authors.lastname: Piccolo
authors.forename: G M
authors.initials: GM
authors.lastname: Fabrizi
authors.forename: T
authors.initials: T
authors.lastname: Cavallaro
authors.forename: F
authors.initials: F
authors.lastname: Taroni
authors.forename: D
authors.initials: D
authors.lastname: Pareyson
mesh_terms: D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D009154:Mutation; D009186:Myelin Sheath / Q000378:metabolism; D012189:Retrospective Studies; D013497:Sural Nerve / Q000473:pathology
chemical_list: D008565:Membrane Proteins; C086745:periaxin