Heterogeneity of axonal pathology in Chinese patients with giant axonal neuropathy.

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.