Document Type : Short Communication


1 Pediatric Growth and Development Research Center, Iran University of Medical Sciences, Tehran, Iran

2 Ali Asghar Children’s Hospital, Iran University of Medical Sciences, Tehran, Iran

3 Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran

4 Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran


Background: Giant axonal neuropathy (GAN) is a very rare fatal neurodegenerative disorder with clinical and allelic heterogeneity. The disease is caused by mutations in the GAN (gigaxonin) gene. Herein, we reported the clinical presentations and results of genetic analysis of the first Iranian GAN case.
Methods: Phenotypic data were obtained by neurologic examination, brain magnetic resonance imaging (MRI), electromyography (EMG), electroencephalography (EEG), and sonography from the proband. Deoxyribonucleic acid (DNA) was isolated from peripheral blood leucocytes and whole exome sequencing (WES) was performed. The candidate variant was screened by Sanger sequencing in the proband and her family members.
Results: The proband was a 7-year-old girl who was admitted with a chief complaint of ataxia, muscle weakness, delayed developmental milestones, and history of psychiatric disorders. She was very moody and had clumsy gait, decreased deep tendon reflexes (DTRs) of lower limbs, and kinky hair. The brain MRI revealed white matter abnormality. The EMG revealed that her disease was compatible with the chronic axonal type of sensorimotor polyneuropathy; however, her EEG was normal. Results of the WES revealed a homozygous variant; c.G778T:p.E260* in the GAN gene, indicating the GAN disorder.
Conclusion: The present study affirmed GAN allelic heterogeneity and resulted in the expansion of the phenotypic spectrum of GAN pathogenic variants. Identification of more families with mutations in GAN gene helps to further understand the molecular basis of the disease and provides an opportunity for genetic counseling especially in the populations with a high degree of consanguineous marriage such as the Iranian population.


  1. Cleveland DW, Yamanaka K, Bomont P. Gigaxonin controls vimentin organization through a tubulin chaperone-independent pathway. Hum Mol Genet 2009; 18(8): 1384-94.
  2. Kang JJ, Liu IY, Wang MB, Srivatsan ES. A review of gigaxonin mutations in giant axonal neuropathy (GAN) and cancer. Hum Genet 2016; 135(7): 675-84.
  3. Kamate M, Ramakrishna S, Kambali S, Mahadevan A. Giant axonal neuropathy: A rare inherited neuropathy with simple clinical clues. BMJ Case Rep 2014; 2014: bcr2014204481.
  4. Incecik F, Herguner OM, Ceylaner S, Zorludemir S, Altunbasak S. Giant axonal disease: Report of eight cases. Brain Dev 2015; 37(8): 803-7.
  5. Nalini A, Gayathri N, Yasha TC, Ravishankar S, Urtizberea A, Huehne K, et al. Clinical, pathological and molecular findings in two siblings with giant axonal neuropathy (GAN): report from India. Eur J Med Genet 2008; 51(5): 426-35.
  6. Ravishankar S, Goel G, Rautenstrauss CP, Nalini A. Spectrum of magnetic resonance imaging findings in a family with giant axonal neuropathy confirmed by genetic studies. Neurol India 2009; 57(2): 181-4.
  7. Demir E, Bomont P, Erdem S, Cavalier L, Demirci M, Kose G, et al. Giant axonal neuropathy: clinical and genetic study in six cases. J Neurol Neurosurg Psychiatry 2005; 76(6): 825-32.
  8. Tandan R, Little BW, Emery ES, Good PS, Pendlebury WW, Bradley WG. Childhood giant axonal neuropathy. Case report and review of the literature. J Neurol Sci 1987; 82(1-3): 205-28.
  9. Johnson-Kerner BL, Roth L, Greene JP, Wichterle H, Sproule DM. Giant axonal neuropathy: An updated perspective on its pathology and pathogenesis. Muscle Nerve 2014; 50(4): 467-76.
  10. Wang J, Ma Q, Cai Q, Liu Y, Wang W, Ren Z. Two novel pathogenic mutations of GAN gene identified in a patient with giant axonal neuropathy. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2016; 33(3): 292-5. [In Chinese].