ArticleJournal of neurology2020
SPG7 mutations in amyotrophic lateral sclerosis: a genetic link to hereditary spastic paraplegia.
Article in Journal of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- The Flail Limb Syndrome.Muscle & nerve · 2026Review
- Genome-wide spectrum of coding DNA variations in Indian patients with amyotrophic lateral sclerosis.Journal of neurology · 2026Article
- Digenic inheritance of mutations in SPG7 and AFG3L2 causes motor neuron and cerebellar disorders.BMC medicine · 2026Article
- Digenic inheritance of mutations in SPG7 and AFG3L2 causes motor neuron and cerebellar disorders.BMC medicine · 2026Article
- Identification of an additional deep intronic splice variant prompts critical evaluation of SPG7 inheritance.Neurogenetics · 2026Article
- Shared burden of ultra-rare genetic variants across a spectrum of motor neuron diseases.Translational neurodegeneration · 2025Article
- Expanding the Phenotypic Spectrum of SPG7 Rare Damaging Variants: Insights From a Hungarian Cohort.Clinical genetics · 2025Article
- Burden of pathogenetic and likely pathogenetic variants in SPG7, SPG11 and AP4 genes in Amyotrophic Lateral Sclerosis. A case-control study.Journal of neurology · 2025Article
- Genetic Basis of Motor Neuron Diseases: Insights, Clinical Management, and Future Directions.International journal of molecular sciences · 2025Review
- Hereditary spastic paraparesis type 18 (SPG18): new ERLIN2 variants in a series of Italian patients, shedding light upon genetic and phenotypic variability.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Undetected Neuromuscular Disease in Patients after Heart Transplantation.International journal of molecular sciences · 2024Article
- Mechanism and treatment of intracerebral hemorrhage focus on mitochondrial permeability transition pore.Frontiers in molecular neuroscience · 2024Review
- Article
- An SPG7 mutation as a novel cause of monogenic progressive muscular atrophy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Article
- Case report: A novelFrontiers in genetics · 2023Article
- A SUMO4 initiator codon variant in amyotrophic lateral sclerosis reduces SUMO4 expression and alters stress granule dynamics.Journal of neurology · 2022Article
- Hereditary Spastic Paraplegia: An Update.International journal of molecular sciences · 2022Review
- HeterozygousGenes · 2021Article
- The Novel Regulatory Role of lncRNA-miRNA-mRNA Axis in Amyotrophic Lateral Sclerosis: An Integrated Bioinformatics Analysis.Computational and mathematical methods in medicine · 2021Article
- Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia (HSP) are motor neuron diseases sharing clinical, pathological, and genetic similarities. While biallelic SPG7 mutations are known to cause recessively inherited HSP, heterozygous SPG7 mutations have repeatedly been identified in HSP and recently also in ALS cases. However, the frequency and clinical impact of rare SPG7 variants have not been studied in a larger ALS cohort. Here, whole-exome (WES) or targeted SPG7 sequencing was done in a cohort of 214 European ALS patients. The consequences of a splice site variant were analyzed on the mRNA level. The resulting protein alterations were visualized in a crystal structure model. All patients were subjected to clinical, electrophysiological, and neuroradiological characterization. In 9 of 214 (4.2%) ALS cases, we identified five different rare heterozygous SPG7 variants, all of which were previously reported in patients with HSP or ALS. All detected SPG7 variants affect the AAA+ domain of the encoded mitochondrial metalloprotease paraplegin and impair its stability or function according to predictions from mRNA analysis or crystal structure modeling. ALS patients with SPG7 mutations more frequently presented with cerebellar symptoms, flail arm or leg syndrome compared to those without SPG7 mutations, and showed a partial clinical overlap with HSP. Brain MRI findings in SPG7 mutation carriers included cerebellar atrophy and patterns suggestive of frontotemporal dementia. Collectively, our findings suggest that SPG7 acts as a genetic risk factor for ALS. ALS patients carrying SPG7 mutations present with distinct features overlapping with HSP, particularly regarding cerebellar findings.
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