ArticleJournal of neurology2014
Mutations in CYP2U1, DDHD2 and GBA2 genes are rare causes of complicated forms of hereditary spastic paraparesis.
Article in Journal of neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 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
- Neurodevelopmental alterations are key drivers of SPG56.Human molecular genetics · 2026Article
- Early-onset hereditary spastic paraplegia type 56 (SPG56): clinical-molecular correlations and functional validation of CYP2U1 variants.BMC medical genomics · 2026Article
- Genotypic and phenotypic spectrum of hereditary spastic paraplegia 56: insights from novel CYP2U1 variants and a literature review.BMC neurology · 2026Review
- DDHD2 provides a flux of saturated fatty acids for neuronal energy and function.Nature metabolism · 2025Article
- Diagnostic journey and genetic analysis of a novel homozygous CYP2U1 mutation causing autosomal recessive spastic paraplegia type 56 (SPG56) in a consanguineous family.BMC neurology · 2025Article
- Hereditary spastic paraparesis type 46 (SPG46): new GBA2 variants in a large Italian case series and review of the literature.Neurogenetics · 2024Review
- Biallelic DDHD2 mutations in patients with adult-onset complex hereditary spastic paraplegia.Annals of clinical and translational neurology · 2023Article
- Co-occurrence ofClinical parkinsonism & related disorders · 2023Article
- Case report: Novel compound heterozygous missense mutations in theFrontiers in pediatrics · 2022Article
- Article
- Lipolysis: cellular mechanisms for lipid mobilization from fat stores.Nature metabolism · 2021Review
- Implication of folate deficiency in CYP2U1 loss of function.The Journal of experimental medicine · 2021Article
- Spastic paraplegia type 46: novel and recurrent GBA2 gene variants in a compound heterozygous Italian patient with spastic ataxia phenotype.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Review
- Impact of Gba2 on neuronopathic Gaucher's disease and α-synuclein accumulation in medaka (Oryzias latipes).Molecular brain · 2021Article
- Recent advances in understanding hereditary spastic paraplegias and emerging therapies.Faculty reviews · 2021Review
- Truncated mutants of beta-glucosidase 2 (GBA2) are localized in the mitochondrial matrix and cause mitochondrial fragmentation.PloS one · 2020Article
- Defining the clinical-genetic and neuroradiological features in SPG54: description of eight additional cases and nine novel DDHD2 variants.Journal of neurology · 2019Article
- Species-specific differences in nonlysosomal glucosylceramidase GBA2 function underlie locomotor dysfunction arising from loss-of-function mutations.The Journal of biological chemistry · 2019Article
- Biochemical Characterization of theInternational journal of molecular sciences · 2018Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Complicated hereditary spastic paraplegias (HSP) are a heterogeneous group of HSP characterized by spasticity associated with a variable combination of neurologic and extra-neurologic signs and symptoms. Among them, HSP with thin corpus callosum and intellectual disability is a frequent subtype, often inherited as a recessive trait (ARHSP-TCC). Within this heterogeneous subgroup, SPG11 and SPG15 represent the most frequent subtypes. We analyzed the mutation frequency of three genes associated with early-onset forms of ARHSP with and without TCC, CYP2U1/SPG56, DDHD2/SPG54 and GBA2/SPG46, in a large population of selected complicated HSP patients by using a combined approach of traditional-based and amplicon-based high-throughput pooled-sequencing. Three families with mutations were identified, one for each of the genes analyzed. Novel homozygous mutations were identified in CYP2U1 (c.1A>C/p.Met1?) and in GBA2 (c.2048G>C/p.Gly683Arg), while the homozygous mutation found in DDHD2 (c.1978G>C/p.Asp660His) had been previously reported in a compound heterozygous state. The phenotypes associated with the CYP2U1 and DDHD2 mutations overlap the SPG56 and the SPG54 subtypes, respectively, with few differences. By contrast, the GBA2 mutated patients show phenotypes combining typical features of both the SPG46 subtype and the recessive ataxia form, with marked intrafamilial variability thereby expanding the spectrum of clinical entities associated with GBA2 mutations. Overall, each of three genes analyzed shows a low mutation frequency in a general population of complicated HSP (<1 % for either CYP2U1 or DDHD2 and approximately 2 % for GBA2). These findings underline once again the genetic heterogeneity of ARHSP-TCC and the clinical overlap between complicated HSP and the recessive ataxia syndromes.
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