Young-Onset Amyotrophic Lateral Sclerosis: Genetic Structure and Phenotypic Features
Introduction. Young-onset amyotrophic lateral sclerosis (yALS) is a rare neurodegenerative disease characterized by the onset of clinical manifestations before the age of 45. The global prevalence, incidence, and genetic structure of yALS remain largely unknown, and the diagnosis is based primarily...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Research Center of Neurology
2025-06-01
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| Series: | Анналы клинической и экспериментальной неврологии |
| Subjects: | |
| Online Access: | https://annaly-nevrologii.com/pathID/article/viewFile/1317/pdf |
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| Summary: | Introduction. Young-onset amyotrophic lateral sclerosis (yALS) is a rare neurodegenerative disease characterized by the onset of clinical manifestations before the age of 45. The global prevalence, incidence, and genetic structure of yALS remain largely unknown, and the diagnosis is based primarily on clinical presentation, neurophysiologic findings, and molecular genetic analysis.
Aim. The aim of this study was to analyze cases of yALS in the Russian Center of Neurology and Neurosciences.
Materials and methods. A total of 365 ALS cases were analyzed, of which 47 (12.8%) patients met the criteria for yALS based on the age of onset and were included in this study. All patients underwent the necessary diagnostic procedures to exclude or establish a diagnosis. The coding sequence of the SOD1 gene was analyzed, and the size of the tandem hexanucleotide repeats (GGGGCC)n in the C9orf72 gene was evaluated. In some cases, massive parallel sequencing was performed.
Results. Mutations in causative ALS genes were detected in 15 (32%) patients: in 15% of cases, variants were found in the coding sequence of the SOD1 gene and 3’ untranslated region, and in 8.7%, hexanucleotide repeat expansions (GGGGCC)n were found in the C9orf72 gene. In addition, in four (8.5%) yALS cases, mutations in the FUS, UBQLN2, and FIG4 genes were identified using massive parallel sequencing.
Conclusion. Early identification of both sporadic and familial forms of yALS and determination of their molecular genetic patterns is critical for timely genetic counseling and identification of potentially treatable etiologies. |
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| ISSN: | 2075-5473 2409-2533 |