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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| Format: | Article |
| Language: | English |
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SpringerOpen
2025-07-01
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| 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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| author | Abdelrahim A. Sadek Mohammed A. Aladawy Tarek M. M. Mansour Ali Farag El Hadad Abd Elaziz Shokry Rin Khang Seung Woo Ryu Elsayed Abdelkreem |
| author_facet | Abdelrahim A. Sadek Mohammed A. Aladawy Tarek M. M. Mansour Ali Farag El Hadad Abd Elaziz Shokry Rin Khang Seung Woo Ryu Elsayed Abdelkreem |
| author_sort | Abdelrahim A. Sadek |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a18a13155d244997bf92fe0dc1636e11 |
| institution | Kabale University |
| issn | 2090-2441 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Medical Human Genetics |
| spelling | doaj-art-a18a13155d244997bf92fe0dc1636e112025-08-20T04:03:01ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412025-07-012611610.1186/s43042-025-00755-yThree siblings with giant axonal neuropathy caused by a novel variant in GAN gene: the first report from EgyptAbdelrahim A. Sadek0Mohammed A. Aladawy1Tarek M. M. Mansour2Ali Farag El Hadad3Abd Elaziz Shokry4Rin Khang5Seung Woo Ryu6Elsayed Abdelkreem7Neuropsychiatry Unit, Department of Pediatrics, Faculty of Medicine, Sohag UniversityNeurology Unit, Department of Pediatrics, Faculty of Medicine, Al-Azhar UniversityDepartment of Radio-Diagnosis, Faculty of Medicine, Al-Azhar UniversityDepartment of Neurology, Faculty of Medicine, Al-Azhar UniversityDepartment of Neurology, Faculty of Medicine, Al-Azhar UniversityDivision of Medical GeneticsDivision of Medical GeneticsDepartment of Pediatrics, Faculty of Medicine, Sohag UniversityAbstract 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.https://doi.org/10.1186/s43042-025-00755-yGiant axonal neuropathyGANGenotypePhenotypeVariant |
| spellingShingle | Abdelrahim A. Sadek Mohammed A. Aladawy Tarek M. M. Mansour Ali Farag El Hadad Abd Elaziz Shokry Rin Khang Seung Woo Ryu Elsayed Abdelkreem Three siblings with giant axonal neuropathy caused by a novel variant in GAN gene: the first report from Egypt Egyptian Journal of Medical Human Genetics Giant axonal neuropathy GAN Genotype Phenotype Variant |
| title | Three siblings with giant axonal neuropathy caused by a novel variant in GAN gene: the first report from Egypt |
| title_full | Three siblings with giant axonal neuropathy caused by a novel variant in GAN gene: the first report from Egypt |
| title_fullStr | Three siblings with giant axonal neuropathy caused by a novel variant in GAN gene: the first report from Egypt |
| title_full_unstemmed | Three siblings with giant axonal neuropathy caused by a novel variant in GAN gene: the first report from Egypt |
| title_short | Three siblings with giant axonal neuropathy caused by a novel variant in GAN gene: the first report from Egypt |
| title_sort | three siblings with giant axonal neuropathy caused by a novel variant in gan gene the first report from egypt |
| topic | Giant axonal neuropathy GAN Genotype Phenotype Variant |
| url | https://doi.org/10.1186/s43042-025-00755-y |
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