ArticleEuropean journal of human genetics : EJHG2017
Massive sequencing of 70 genes reveals a myriad of missing genes or mechanisms to be uncovered in hereditary spastic paraplegias.
Article in European journal of human genetics : EJHG, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Genotype-phenotype associations in hereditary spastic paraplegia: a systematic review and meta-analysis on 13,570 patients.Journal of neurology · 2021Pooled it
- Expanding the genetic and clinical landscapes of hereditary spastic paraplegia (HSP): a cohort study of 103 families.Orphanet journal of rare diseases · 2026Article
- The Genetic Landscape of Hereditary Spastic Paraplegia in Greece.Clinical genetics · 2026Article
- Children with suspected hereditary spastic paraplegia clearly benefit from whole exome analysis.Human genomics · 2026Article
- High Genetic Diagnostic Yield for Patients with Rare Movement Disorders at a Single-Center Neurogenetics Clinic.Movement disorders clinical practice · 2025Article
- Hereditary spastic paraplegias: When to expect bladder dysfunction a genetic and urodynamic study.European journal of neurology · 2025Article
- Case Report: Hereditary spastic paraplegia associated with monoallelic variant in the motor domain of KIF1A.Frontiers in human neuroscience · 2025Article
- Clinical phenotyping and genetic diagnosis of a large cohort of Sudanese families with hereditary spinocerebellar degenerations.European journal of human genetics : EJHG · 2024Article
- Patients with complex and very-early-onset ATL1-related spastic paraplegia offer insights on genotype/phenotype correlations and support for autosomal recessive forms of SPG3A.Journal of neurology · 2024Article
- 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
- Unexpected complexity in the molecular diagnosis of spastic paraplegia 11.Molecular genetics & genomic medicine · 2024Article
- Hereditary spastic paraparesis type 46 (SPG46): new GBA2 variants in a large Italian case series and review of the literature.Neurogenetics · 2024Review
- Power of NGS-based tests in HSP diagnosis: analysis of massively parallel sequencing in clinical practice.Neurogenetics · 2023Review
- Computational study of the motor neuron protein KIF5A to identify nsSNPs, bioactive compounds, and its key regulators.Frontiers in genetics · 2023Article
- Reduced penetrance of an eastern French mutation in ATL1 autosomal-dominant inheritance (SPG3A): extended phenotypic spectrum coupled with brainNeurogenetics · 2022Article
- Article
- A rigorousFrontiers in molecular neuroscience · 2022Article
- A novel variant ofAnnals of translational medicine · 2022Article
- Review
- Evidence of mosaicism in SPAST variant carriers in four French families.European journal of human genetics : EJHG · 2021Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hereditary spastic paraplegias (HSP) are neurodegenerative disorders characterized by lower limb spasticity and weakness that can be complicated by other neurological or non-neurological signs. Despite a high genetic heterogeneity (>60 causative genes), 40-70% of the families remain without a molecular diagnosis. Analysis of one of the pioneer cohorts of 193 HSP families generated in the early 1990s in Portugal highlighted that SPAST and SPG11 are the most frequent diagnoses. We have now explored 98 unsolved families from this series using custom next generation sequencing panels analyzing up to 70 candidate HSP genes. We identified the likely disease-causing variant in 20 of the 98 families with KIF5A being the most frequently mutated gene. We also found 52 variants of unknown significance (VUS) in 38% of the cases. These new diagnoses resulted in 42% of solved cases in the full Portuguese cohort (81/193). Segregation of the variants was not always compatible with the presumed inheritance, indicating that the analysis of all HSP genes regardless of the inheritance mode can help to explain some cases. Our results show that there is still a large set of unknown genes responsible for HSP and most likely novel mechanisms or inheritance modes leading to the disease to be uncovered, but this will require international collaborative efforts, particularly for the analysis of VUS.
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