ArticleNeurogenetics2018
The impact of next-generation sequencing on the diagnosis of pediatric-onset hereditary spastic paraplegias: new genotype-phenotype correlations for rare HSP-related genes.
Article in Neurogenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
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Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Monoallelic KIF1A-related disorders: a multicenter cross sectional study and systematic literature review.Journal of neurology · 2022Pooled it
- Genotype-phenotype associations in hereditary spastic paraplegia: a systematic review and meta-analysis on 13,570 patients.Journal of neurology · 2021Pooled it
- Hereditary spastic paraplegia: from decades of therapy to future innovations.Therapeutic advances in neurological disorders · 2026Review
- DDHD2 provides a flux of saturated fatty acids for neuronal energy and function.Nature metabolism · 2025Article
- Distinct Clinical Phenotypes in KIF1A-Associated Neurological Disorders Result from Different Amino Acid Substitutions at the Same Residue in KIF1A.Biomolecules · 2025Article
- Expanding the phenotypic spectrum ofCurrent journal of neurology · 2025Article
- Association of novel ERLIN2 gene variants with hereditary spastic paraplegia.Human genome variation · 2025Article
- 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
- Cryo-EM unveils kinesin KIF1A's processivity mechanism and the impact of its pathogenic variant P305L.Nature communications · 2024Article
- Biallelic DDHD2 mutations in patients with adult-onset complex hereditary spastic paraplegia.Annals of clinical and translational neurology · 2023Article
- Power of NGS-based tests in HSP diagnosis: analysis of massively parallel sequencing in clinical practice.Neurogenetics · 2023Review
- Fatty Acid 2-Hydroxylase and 2-Hydroxylated Sphingolipids: Metabolism and Function in Health and Diseases.International journal of molecular sciences · 2023Review
- Genetic and clinical features of pediatric-onset hereditary spastic paraplegia: a single-center study in Japan.Frontiers in neurology · 2023Article
- Biallelic Variants in the Ectonucleotidase ENTPD1 Cause a Complex Neurodevelopmental Disorder with Intellectual Disability, Distinct White Matter Abnormalities, and Spastic Paraplegia.Annals of neurology · 2022Article
- Review
- Case report: Novel compound heterozygous missense mutations in theFrontiers in pediatrics · 2022Article
- A rigorousFrontiers in molecular neuroscience · 2022Article
- Single-Molecule Studies on the Motion and Force Generation of the Kinesin-3 Motor KIF1A.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Genotype and defects in microtubule-based motility correlate with clinical severity inHGG advances · 2021Article
- Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlations.Neurogenetics · 2021Article
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hereditary spastic paraplegias (HSP) are clinical and genetic heterogeneous diseases with more than 80 disease genes identified thus far. Studies on large cohorts of HSP patients showed that, by means of current technologies, the percentage of genetically solved cases is close to 50%. Notably, the percentage of molecularly confirmed diagnoses decreases significantly in sporadic patients. To describe our diagnostic molecular genetic approach on patients with pediatric-onset pure and complex HSP, 47 subjects with HSP underwent molecular screening of 113 known and candidate disease genes by targeted capture and massively parallel sequencing. Negative cases were successively analyzed by multiplex ligation-dependent probe amplification (MLPA) analysis for the SPAST gene and high-resolution SNP array analysis for genome-wide CNV detection. Diagnosis was molecularly confirmed in 29 out of 47 (62%) patients, most of whom had clinical diagnosis of cHSP. Although SPG11 and SPG4 remain the most frequent cause of, respectively, complex and pure HSP, a large number of pathogenic variants were disclosed in POLR3A, FA2H, DDHD2, ATP2B4, ENTPD1, ERLIN2, CAPN1, ALS2, ADAR1, RNASEH2B, TUBB4A, ATL1, and KIF1A. In a subset of these disease genes, phenotypic expansion and novel genotype-phenotype correlations were recognized. Notably, SNP array analysis did not provide any significant contribution in increasing the diagnostic yield. Our findings document the high diagnostic yield of targeted sequencing for patients with pediatric-onset, complex, and pure HSP. MLPA for SPAST and SNP array should be limited to properly selected cases based on clinical suspicion.
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