Four novel cases of periaxin-related neuropathy and review of the literature

C. Marchesi, M. Milani, M. Morbin, M. Cesani, G. Lauria, V. Scaioli, G. Piccolo, G. M. Fabrizi, T. Cavallaro, F. Taroni, D. Pareyson

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1830-1838
Number of pages9
Issue number20
Publication statusPublished - Nov 16 2010

ASJC Scopus subject areas

  • Clinical Neurology


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