Frequency and phenotype of SPG11 and SPG15 in complicated hereditary spastic paraplegia
Open accessAbstract
BACKGROUND: Hereditary spastic paraplegias (HSP) are clinically and genetically highly heterogeneous. Recently, two novel genes, SPG11 (spatacsin) and SPG15 (spastizin), associated with autosomal recessive HSP, were identified. Clinically, both are characterised by complicated HSP and a rather similar phenotype consisting of early onset spastic paraplegia, cognitive deficits, thin corpus callosum (TCC), peripheral neuropathy and mild cerebellar ataxia. OBJECTIVE: To compare the frequency of SPG11 and SPG15 in patients with early onset complicated HSP and to further characterise the phenotype of SPG11 and SPG15. RESULTS: A sample of 36 index patients with early onset complicated HSP and a family history compatible with autosomal recessive inheritance was collected and screened for mutations in SPG11 and SPG15. Overall frequency of SPG11 was 14% (5/36) but was considerably higher in patients with TCC (42%). One patient with mental retardation and thinning of the corpus callosum was compound heterozygous for two novel SPG15 mutations. Additionally, several new polymorphisms and sequence variants of unknown significance have been identified in the SPG15 gene. CONCLUSIONS: TCC seems to be the best phenotypic predictor for SPG11 as well as SPG15. No clinical features could discriminate between SPG11 and SPG15. Therefore, priority of genetic testing should be driven by mutation frequency that appears to be substantially higher in SPG11 than in SPG15.
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Complex neurodegenerative disorders with systemic abnormalities, such as ARSACS and certain forms of HSP, would also benefit from a gene therapeutic approach developed from any of the methods discussed in this review.
“Yet, complex neurodegenerative disorders with systemic abnormalities, such as Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) [128] and certain forms of Hereditary Spastic Paraplegia (HSP, including SPG11 and SPG15-HSPs) [129], would also benefit from a gene therapeutic approach developed from any of the methods discussed in this review.”
From Circumventing the packaging limit of AAV-mediated gene replacement therapy for neurological disorders (2022) · cites this paper as [129]
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- Durr A. Genetic testing for the spastic paraplegias: drowning by numbers. Neurology 2008;71(4):236-238.
- Tsaousidou MK, Ouahchi K, Warner TT, et al. Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration. Am J Hum Genet 2008;82(2):510-515.
- Hehr U, Bauer P, Winner B, et al. Long-term course and mutational spectrum of spatacsin-linked spastic paraplegia. Ann Neurol 2007;62(6):656-665.
- Hanein S, Martin E, Boukhris A, et al. Identification of the SPG15 gene, encoding spastizin, as a frequent cause of complicated autosomal-recessive spastic paraplegia, including Kjellin syndrome. Am J Hum Genet 2008;82(4):992-1002.
- Boukhris A, Stevanin G, Feki I, et al. Hereditary spastic paraplegia with mental impairment and thin corpus callosum in Tunisia: SPG11, SPG15, and further genetic heterogeneity. Arch Neurol 2008;65(3):393-402.
- Elleuch N, Bouslam N, Hanein S, et al. Refinement of the SPG15 candidate interval and phenotypic heterogeneity in three large Arab families. Neurogenetics 2007;8(4):307-315.
- Denora PS, Muglia M, Casali C, et al. Spastic paraplegia with thinning of the corpus callosum and white matter abnormalities: Further mutations and relative frequency in ZFYVE26/SPG15 in the Italian population. J Neurol Sci 2009;277(1-2):22-25.
- Schule R, Holland-Letz T, Klimpe S, et al. The Spastic Paraplegia Rating Scale (SPRS): a reliable and valid measure of disease severity. Neurology 2006;67(3):430-434.
- Reese MG, Eeckman FH, Kulp D, et al. Improved splice site detection in Genie. J Comput Biol 1997;4(3):311-323.
- Blom N, Gammeltoft S, Brunak S. Sequence and structure-based prediction of eukaryotic protein phosphorylation sites. J Mol Biol 1999;294(5):1351-1362.
- Sunyaev S, Ramensky V, Koch I, et al. Prediction of deleterious human alleles. Hum Mol Genet 2001;10(6):591-597.
- Hebsgaard SM, Korning PG, Tolstrup N, et al. Splice site prediction in Arabidopsis thaliana pre-mRNA by combining local and global sequence information. Nucleic Acids Res 1996;24(17):3439-3452.
- Hughes CA, Byrne PC, Webb S, et al. SPG15, a new locus for autosomal recessive complicated HSP on chromosome 14q. Neurology 2001;56(9):1230-1233.
- Boukhris A, Feki I, Denis E, et al. Spastic paraplegia 15: linkage and clinical description of three Tunisian families. Mov Disord 2008;23(3):429-433.
- Zarei M, Johansen-Berg H, Smith S, et al. Functional anatomy of interhemispheric cortical connections in the human brain. J Anat 2006;209(3):311-320.
- Elleuch N, Depienne C, Benomar A, et al. Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary spastic paraplegia. Neurology 2006;66(5):654-659.
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Marrone, L., Marchi, P. M., & Azzouz, M. (2022) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2022.2012148 · Cited by 56 · see citing works
“[128] and certain forms of Hereditary Spastic Paraplegia (HSP, including SPG11 and SPG15-HSPs) [129], would also benefit from a gene therapeutic approach developed from any of the methods discussed in this review.”
- Authors
- Schule, R., Schlipf, N., Synofzik, M., Klebe, S., Klimpe, S., Hehr, U., Winner, B., Lindig, T., Dotzer, A., Riess, O., Winkler, J., Schols, L., & Bauer, P.
- Affiliations
- University of Tübingen (DE)
- Hertie Institute for Clinical Brain Research (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- Johannes Gutenberg University Mainz (DE)
- University of Regensburg (DE)
- Pontifícia Universidade Católica do Paraná (BR)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2009-11-16
- Volume
- 80
- Issue
- 12
- Pages
- 1402-1404
- ISSN
- 0022-3050 (ISSN-L)
- OpenAlex
- W2157532809
- Cited by
- 80
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 1 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 7 · 2017: 4 · 2016: 9 · 2015: 10 · 2014: 9 · 2013: 6 · 2012: 6
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- green
- hal.science
- Licence
- other-oa
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- E-Rare
- Bundesministerium für Bildung und Forschung (01GM0603, 01GM0807)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- hereditary spastic paraplegia, SPG11, spatacsin, SPG15, autosomal recessive inheritance, thin corpus callosum, genotype-phenotype correlation, mutation frequency, compound heterozygosity, cognitive impairment, peripheral neuropathy, cerebellar ataxia, genetic testing, novel polymorphisms
- MeSH terms
- Adolescent, Adult, Carrier Proteins, Corpus Callosum, Female, Gene Frequency, Genes, Recessive, Humans, Male, Intellectual Disability, Mutation, Phenotype, Polymorphism, Genetic, Proteins, Spastic Paraplegia, Hereditary, Young Adult, Genetic Association Studies
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