Three siblings with giant axonal neuropathy caused by a novel variant in GAN gene: the first report from Egypt

Abstract Background Giant axonal neuropathy (GAN) is a rare inherited neurodegenerative disease that affects the peripheral and central nervous systems. Herein, we describe three Egyptian siblings with GAN who showed differences in clinical severity. Case Presentation. Case 1 had slowly progressive...

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Main Authors: Abdelrahim A. Sadek, Mohammed A. Aladawy, Tarek M. M. Mansour, Ali Farag El Hadad, Abd Elaziz Shokry, Rin Khang, Seung Woo Ryu, Elsayed Abdelkreem
Format: Article
Language:English
Published: SpringerOpen 2025-07-01
Series:Egyptian Journal of Medical Human Genetics
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Online Access:https://doi.org/10.1186/s43042-025-00755-y
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Summary:Abstract Background Giant axonal neuropathy (GAN) is a rare inherited neurodegenerative disease that affects the peripheral and central nervous systems. Herein, we describe three Egyptian siblings with GAN who showed differences in clinical severity. Case Presentation. Case 1 had slowly progressive sensorimotor polyneuropathy starting from 6 years of age with lack of remarkable central nervous system (CNS) involvement till age of 14 years. In contrast, case 2 showed early-onset neurodevelopmental delay, rapidly progressive course, and significant CNS manifestations. Case 3 had an intermediate phenotype. The extent of brain imaging abnormalities paralleled the clinical severity as case 1 had only moderate white matter changes while case 2 showed extensive white matter lesions, ventriculomegaly, and atrophic changes. Whole-exome sequencing revealed a novel homozygous nonsense GAN variant c.918G > A (p.Trp306Ter). Conclusion This is the first case report of GAN from Egyptian populations, which expands the spectrum of disease-causing variants in the GAN gene and underscores the clinical heterogeneity of this disease even among patients sharing the same genotype and environmental conditions.
ISSN:2090-2441