Heterogeneity of axonal pathology in Chinese patients with giant axonal neuropathy

Muscle Nerve. 2014 Aug;50(2):200-5. doi: 10.1002/mus.24130. Epub 2014 May 17.

Abstract

Introduction: Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the GAN gene. Herein we report ultrastructural changes in Chinese patients with GAN.

Methods: General clinical assessment, sural nerve biopsy, and genetic analysis were performed.

Results: Sural biopsy revealed giant axons in 3 patients, 2 with a mild phenotype and 1 with a classical phenotype. Ultrastructurally, all patients had giant axons filled with closely packed neurofilaments. In addition, the classical patient had some axons containing irregular tubular-like structures. GAN mutation analysis revealed novel compound heterozygous c.98A>C and c.158C>T mutations in the BTB domain in 1 mild patient, a novel homozygous c.371T>G mutation in the BACK domain in another mild patient, and a novel c.1342G>T homozygous mutation in the Kelch domain in the classical patient.

Conclusion: Closely packed neurofilaments in giant axons are common pathological changes in Chinese patients with GAN, whereas irregular tubular-like structures appear in the classical type of this neuropathy.

Keywords: gene mutation; giant axonal neuropathy; gigaxonin protein; neurofilament protein; tubular-like structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain / pathology
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics
  • Electromyography
  • Female
  • Giant Axonal Neuropathy / diagnosis
  • Giant Axonal Neuropathy / genetics*
  • Giant Axonal Neuropathy / pathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mutation
  • Sural Nerve / pathology*
  • Transcription Factors / genetics
  • Young Adult

Substances

  • BTBD1 protein, human
  • DNA-Binding Proteins
  • Transcription Factors