title: Heterogeneity of axonal pathology in Chinese patients with giant axonal neuropathy.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Danhua
authors.initials: D
authors.lastname: Zhao
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: He
authors.initials: H
authors.lastname: Lv
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Lingchao
authors.initials: L
authors.lastname: Meng
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D004576:Electromyography; D005260:Female; D056768:Giant Axonal Neuropathy / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D013497:Sural Nerve / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult
chemical_list: C429757:BTBD1 protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors
keywords: gene mutation; giant axonal neuropathy; gigaxonin protein; neurofilament protein; tubular-like structure