ArticleAmerican journal of human genetics2002
Infantile-onset ascending hereditary spastic paralysis is associated with mutations in the alsin gene.
Article in American journal of human genetics, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 223 citations in OpenAlex.
- Novel mutations in the ALDH18A1 gene in complicated hereditary spastic paraplegia with cerebellar ataxia and cognitive impairment.Journal of human genetics · 2018Trial
- MK4 Repositioning for IAHSP: OvercomingACS chemical neuroscience · 2026Article
- Elevated Plasma Neurofilament Light Chain Levels in Children with Infantile-Onset Ascending Hereditary Spastic Paralysis.Movement disorders clinical practice · 2025Observational
- Inflammatory cytokine upd3 induces axon length-dependent synapse removal by glia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genetic Basis of Motor Neuron Diseases: Insights, Clinical Management, and Future Directions.International journal of molecular sciences · 2025Review
- Clinical features and molecular genetic investigation of infantile-onset ascending hereditary spastic paralysis (IAHSP) in two Chinese siblings caused by a novel splice site ALS2 variation.BMC medical genomics · 2024Article
- Primary Lateral Sclerosis: An Overview.Journal of clinical medicine · 2024Review
- Review
- Personalized Treatment for Infantile Ascending Hereditary Spastic Paralysis Based on In Silico Strategies.Molecules (Basel, Switzerland) · 2022Article
- ALS2-related disorders in Spanish children: a severely affected case of infantile ascending spastic paraplegia due to homozygous R704X mutation.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Article
- 2-Year-Old and 3-Year-Old Italian ALS Patients with NovelMetabolites · 2022Article
- Review
- Infantile Ascending Hereditary Spastic Paralysis with Extrapyramidal and Extraocular Manifestations Associated with a NovelMovement disorders clinical practice · 2022Article
- Review
- ALS2 regulates endosomal trafficking, postsynaptic development, and neuronal survival.The Journal of cell biology · 2021Article
- Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview.Frontiers in molecular biosciences · 2021Review
- Better understanding the neurobiology of primary lateral sclerosis.Amyotrophic lateral sclerosis & frontotemporal degeneration · 2020Review
- Description of combined ARHSP/JALS phenotype in some patients with SPG11 mutations.Molecular genetics & genomic medicine · 2020Article
- A Systematic Review of Genotype-Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS.Journal of personalized medicine · 2020Review
- Membrane trafficking in health and disease.Disease models & mechanisms · 2020Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We studied 15 patients, from 10 families, who presented with severe spastic paralysis with an infantile onset and an ascending progression. Spastic paraplegia began during the first 2 years of life and extended to upper limbs within the next few years. During the first decade of life, the disease progressed to tetraplegia, anarthria, dysphagia, and slow eye movements. Overall, the disease was compatible with long survival. Signs of lower motor-neuron involvement were never observed, whereas motor-evoked potentials and magnetic resonance imaging demonstrated a primitive, pure degeneration of the upper motor neurons. Genotyping and linkage analyses demonstrated that this infantile-onset ascending hereditary spastic paralysis (IAHSP) is allelic to the condition previously reported as juvenile amyotrophic lateral sclerosis at the ALS2 locus on chromosome 2q33-35 (LOD score 6.66 at recombination fraction 0). We analyzed ALS2, recently found mutated in consanguineous Arabic families presenting either an ALS2 phenotype or juvenile-onset primary lateral sclerosis (JPLS), as a candidate gene. In 4 of the 10 families, we found abnormalities: three deletions and one splice-site mutation. All the mutations lead to a truncated alsin protein. In one case, the mutation affected both the short and the long alsin transcript. In the six remaining families, absence of cDNA ALS2 mutations suggests either mutations in regulatory ALS2 regions or genetic heterogeneity, as already reported in JPLS. Alsin mutations are responsible for a primitive, retrograde degeneration of the upper motor neurons of the pyramidal tracts, leading to a clinical continuum from infantile (IAHSP) to juvenile forms with (ALS2) or without (JPLS) lower motor-neuron involvement. Further analyses will determine whether other hereditary disorders with primitive involvement of the central motor pathways, as pure forms of spastic paraplegia, could be due to alsin dysfunction.
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