Giant axonal neuropathy: a rare inherited neuropathy with a novel mutation

We present a 7.5-year-old boy born to a family from the Iranian Azeri Turkish ethnic group with a consanguineous marriage who presents with a unique set of symptoms, suggesting Giant Axonal Neuropathy. He achieved independent walking at age 3 years, with frequent falling during running. Physical and...

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Bibliographic Details
Published in:Neurogenetics 2024-11, Vol.26 (1), p.11
Main Authors: Poorshiri, Bita, Jabbarpour, Neda, Barzegar, Mohammad, Bonyadi, Mortaza, Ebadi, Zakiyeh
Format: Article
Language:English
Subjects:
Atrophy
Bioinformatics
Brief Communication
Child
Consanguinity
Cytoskeletal Proteins
Exome Sequencing
Genomic analysis
Giant Axonal Neuropathy - genetics
Giant Axonal Neuropathy - pathology
Homozygote
Human Genetics
Humans
Iran
Male
Medicine
Medicine & Public Health
Minority & ethnic groups
Molecular Medicine
Mutation - genetics
Neurology
Neuropathy
Neurosciences
Pathogenicity
Pedigree
Population studies
Segregation
Whole genome sequencing
Citations: Items that this one cites
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Summary:We present a 7.5-year-old boy born to a family from the Iranian Azeri Turkish ethnic group with a consanguineous marriage who presents with a unique set of symptoms, suggesting Giant Axonal Neuropathy. He achieved independent walking at age 3 years, with frequent falling during running. Physical and neurological examinations reveal curly blond hair, generalized muscle atrophy, slow speech and difficulty swallowing solid food, foot drop, pes cavus, hammertoe deformities; reduced deep tendon reflexes, clumsy gait, impaired sense of position, and intention tremors. This comprehensive report significantly expands the clinical and mutational spectrum of Giant Axonal Neuropathy. Whole Exome Sequencing (WES) analysis revealed a novel homozygous variant ( NC_000016.10 ( NM_022041.3):c.2T > C ) in the GAN gene, confirmed by Sanger sequencing. Segregation analysis showed that the parents were heterozygous for the variant. The variant was absent in a cohort of 430 healthy individuals from the same ethnic group and in other published population databases such as GenomAD and the 1000 Genome. The clinical manifestations, segregation analysis, population study, and bioinformatics analysis collectively confirm the pathogenicity of variant.
ISSN:1364-6745
1364-6753
1364-6753
DOI:10.1007/s10048-024-00790-8