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Case report: A novel WASHC5 variant altering mRNA splicing causes spastic paraplegia in a patient
Open accessAbstract
Background: Hereditary spastic paraplegia (HSP) is a progressive upper-motor neurodegenerative disease. Mutations in the WASHC5 gene are associated with autosomal dominant HSP, spastic paraplegia 8 (SPG8). However, due to the small number of reported cases, the exact mechanism remains unclear. Method: We report a Chinese family with HSP. The proband was referred to our hospital due to restless leg syndrome and insomnia. The preliminary clinical diagnosis of the proband was spastic paraplegia. Whole-exome sequencing (WES) and RNA splicing analysis were conducted to evaluate the genetic cause of the disease in this family. Results: A novel splice-altering variant (c.712–2A>G) in the WASHC5 gene was detected and further verified by RNA splicing analysis and Sanger sequencing. Real-time qPCR analysis showed that the expression of genes involved in the Wiskott–Aldrich syndrome protein and SCAR homolog (WASH) complex and endosomal and lysosomal systems was altered due to this variant. Conclusion: A novel heterozygous splice-altering variant (c.712–2A>G) in the WASHC5 gene was detected in a Chinese family with HSP. Our study provided data for genetic counseling to this family and offered evidence that this splicing variant in the WASHC5 gene is significant in causing HSP.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This case report identifies a novel heterozygous WASHC5 splice variant (c.712–2A>G) in a Chinese family with hereditary spastic paraplegia, molecularly diagnosing the proband with SPG8. RNA analysis shows the variant causes intron 6 retention and a 10-amino-acid insertion, with altered expression of WASH complex, endosomal, and lysosomal genes.
Key findings
- A novel heterozygous WASHC5 variant, chr8:126088744T>C / NM_014846.4:c.712–2A>G, was detected in the proband and classified as “likely pathogenic” by ACMG criteria (PVS1 and PM2); it was absent from 1,000G, ExAC, and ESP6500 and had a GnomAD frequency of 0.000004 (1/251100).
- RNA splicing analysis showed the variant produced a 337-nucleotide aberrant PCR product versus the expected 307-nucleotide wild-type product, retaining 30 nucleotides of intron 6 and inserting 10 aberrant amino acids (LSRGVVLTLR) at position 237, resulting in an abnormally prolonged protein of 1,169 aa.
- Co-segregation analysis found the variant absent in healthy family members II-1, III-1, III-2, and IV-1; the proband was diagnosed with SPG8.
- qPCR in peripheral blood lymphocytes showed significantly decreased WASHC1 and WASHC3 mRNA, significantly increased VCP mRNA, significantly changed ARPC3 expression, and significantly upregulated endosomal-related genes (RAB5A, RAB5C, RAB11A, RAB11B) and lysosome-related genes (LAPTM4B, LAPTM5) in the proband compared with healthy family members.
Methods
- Case report of a Chinese family; the proband was a 58-year-old woman referred for restless legs syndrome and insomnia, with preliminary clinical diagnosis of spastic paraplegia.
- Whole-exome sequencing yielded 10.21 GB data with 98.1% coverage of target regions and 96.0% of target covered over ×10; variants were filtered using a movement-disorders gene panel, and Sanger sequencing was performed in available family members.
- RNA splicing analysis used peripheral blood cDNA with PCR, agarose gel electrophoresis, and Sanger sequencing; real-time qPCR measured mRNA from peripheral blood lymphocytes of the proband (II-3) and two healthy female family members (II-1 and III-2), normalized to ACTB using the 2−ΔΔCT method, with unpaired Student’s t-test and p < 0.05 considered significant.
Limitations
- The paper states that deceased family members I-2 and II-2 were considered affected by relatives but could not be tested because DNA was unavailable, and the proband’s younger son III-3 died in a car crash at age 15 before any possible onset, so his genetic status was unknown.
- The paper states that inadequate patient cooperation during testing prevented other diagnostic data from being obtained, and that additional functional analyses, such as whether the variant affects protein stability and half-life, are recommended; the endosomal/lysosomal involvement is described as a hypothesis that requires further study.
- Evident from the text: this is a single-family case report with qPCR performed in only three female subjects, no independent replication or protein-level functional validation, and no direct testing of the deceased affected relatives.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Claims the paper makes
0 of 17 cited sources checked · 0 supported · 0 flagged
- Findingown data
SWISS-MODEL predicted that the splice variant may lead to an insertion of 10 amino acids behind Q237 in the mutated WASHC5 protein.
“SWISS-MODEL software (https://swissmodel.expasy.org/) showed that the splice variant may lead to an insertion of 10 amino acids behind Q237 in the mutated WASHC5 protein (Figure 2A).”
Quote in the paperSubstantial claim - Findingnone given
There was no evidence indicating the presence of peripheral neuropathy in the proband.
“There was no evidence indicating the presence of peripheral neuropathy in the proband.”
Quote in the paperNot a substantial claim - Findingcitation
Under ACMG guidelines with evidence PVS1 and PM2, the c.712-2A>G variant is classified as likely pathogenic.
“According to the American College of Medical Genetics and Genomics (ACMG) guidelines (Miller et al., 2021), with the following evidence: PVS1 and PM2, the c.712–2A>G variant is classified as “likely pathogenic.””
Quote in the paperSubstantial claim0 of 1 sources checked- cites Miller et al., 2021 source
- Findingown data
The proband showed asymmetric spasticity of a single lower extremity.
“Notably, our proband showed asymmetric spasticity of a single lower extremity.”
Quote in the paperSubstantial claim - Findingown data
The proband had lower mRNA level of the ARPC3 gene compared with healthy family members.
“The results showed that there was a significant change in the proband’s ARPC3 gene expression (Figure 2E).”
- Also stated in: § Discussion · plain
“we found that the proband with the splice variant had a higher mRNA level of the VCP gene and lower mRNA level of the ARPC3 gene.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingreasoning
The c.712-2A>G variant is the fourth splice-altering variant in the WASHC5 gene in a HSP patient.
“Here, we report the fourth splice-altering variant in the WASHC5 gene in a HSP patient.”
Quote in the paperNot a substantial claim - Findingown data
No changes in RAB4A, LAMP1, and LAMP2 mRNA levels were detected.
“No changes in RAB4A, LAMP1, and LAMP2 mRNA levels were detected (Figures 2F, G).”
Quote in the paperNot a substantial claim - Findingown data
Co-segregation analysis showed that the c.712-2A>G variant was not present in the healthy family members II-1, III-1, III-2, and IV-1.
“Co-segregation analysis showed that the c.712–2A>G variant was not present in the healthy members (II-1, III-1, III-2, and IV-1) in this family (Figure 1G).”
Quote in the paperSubstantial claim - Findingown data
The proband had a reduction in the amplitude of the action potential of the left common peroneal nerve.
“The findings indicated a reduction in the amplitude of the action potential of the left common peroneal nerve in the proband.”
Quote in the paperNot a substantial claim - Findingown data
The c.712-2A>G variant is predicted to be pathogenic by MutationTaster.
“The c.712–2A>G variant is predicted to be pathogenic by MutationTaster (http://www.mutationtaster.org/).”
Quote in the paperSubstantial claim - Findingown data
Expression of endosomal-related genes RAB5A, RAB5C, RAB11A, and RAB11B and lysosome-related genes LAPTM4B and LAPTM5 was significantly upregulated in the proband compared with healthy family members.
“In addition, the transcriptional analysis revealed that the expression of endosomal-related genes (RAB5A, RAB5C, RAB11A, and RAB11B) and lysosome-related genes (LAPTM4B and LAPTM5) was significantly upregulated in the proband when compared to the healthy family members (Figures 2F, G).”
Quote in the paperNot a substantial claim - Findingown data
ConSurf Server predicted that the 10 inserted amino acids are in the conserved region of the WASHC5 protein.
“ConSurf Server software (http://consurf.tau.ac.il/) predicted that the 10 amino acids were inserted in the conserved region of the WASHC5 protein (Figure 2B).”
Quote in the paperNot a substantial claim - Findingown data
Compared with healthy family members, the mRNA level of the VCP gene was significantly increased in the proband.
“Compared with the healthy family members, the mRNA level of the VCP gene was significantly increased in the proband.”
Quote in the paperNot a substantial claim - Findingown data
The proband's offspring have not inherited the c.712-2A>G variant.
“Furthermore, we have determined that the proband’s offspring have not inherited the c.712–2A>G variant, indicating that its genetic impact can be excluded in future prenatal diagnostics.”
Quote in the paperSubstantial claim - Findingown data
The c.712-2A>G variant causes retention of 30 nucleotides of intron 6 of WASHC5 in the mutant transcript.
“The Sanger sequencing of the mutant transcript confirmed that 30 nucleotides of intron 6 of the WASHC5 are preserved in the open-reading frame.”
Quote in the paperSubstantial claim - Findingown data
MetaDome indicated that the affected residues are located in the slightly intolerant region of the WASHC5 protein.
“MetaDome software (https://stuart.radboudumc.nl/metadome/dashboard) indicated that the affected residues are located in the slightly intolerant region of the WASHC5 protein (Figure 2C).”
Quote in the paperNot a substantial claim - Findingown data
qPCR showed that expression of WASH complex member-related genes WASHC1 and WASHC3 was significantly decreased in the proband compared with healthy family members.
“qPCR analysis indicated that the expression of WASH complex member-related genes in the proband, including WASHC1 and WASHC3, was significantly decreased when compared with the healthy family members (Figure 2D).”
Quote in the paperSubstantial claim - Findingown data
A novel heterozygous splice-altering variant c.712-2A>G in the WASHC5 gene was detected in the proband.
“A novel splice-altering variant (c.712–2A>G) in the WASHC5 gene was detected and further verified by RNA splicing analysis and Sanger sequencing.”
- Also stated in: § Genetic analysis · plain
“After analysis, a heterozygous splice variant (chr8:126088744T>C/NM_014846.4: c.712–2A>G) in WASHC5 was identified in the proband (Figure 1I).”
- Also stated in: § Conclusion · plain
“A novel heterozygous splice variant (c.712–2A>G) of the WASHC5 gene was detected.”
Quote in the paperSubstantial claim - Also stated in: § Genetic analysis · plain
- Interpretationown data
The c.712-2A>G variant is significant in causing HSP.
“Our study provided data for genetic counseling to this family and offered evidence that this splicing variant in the WASHC5 gene is significant in causing HSP.”
- Also stated in: § Discussion · plain
“our findings offer more evidence that splice variants of the WASHC5 gene are significant in HSP.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Interpretationreasoning
The proband's asymmetric spasticity of a single lower extremity expands the phenotypic spectrum of SPG8.
“Thus, our proband’s phenotype expands the phenotypic spectrum of SPG8.”
Quote in the paperSubstantial claim - Interpretationown data
The proband was molecularly diagnosed with SPG8.
“Consequently, the diagnosis of the proband was determined to be SPG8 type.”
- Also stated in: § Conclusion · plain
“The proband was further molecularly diagnosed with SPG8.”
Quote in the paperSubstantial claim- Rests on an assumption: Mutations in the WASHC5 gene can lead to SPG8.
- Also stated in: § Conclusion · plain
- Interpretationown data
The expression changes indicate that both endosomal and lysosomal systems of the proband could be affected by the c.712-2A>G variant.
“These results indicate that both endosomal and lysosomal systems of the proband could be affected by the c.712–2A>G variant. This hypothesis will only be proven by further study.”
Quote in the paperSubstantial claim - Interpretationreasoning
The disease was probably dominantly inherited based on the proband's father having similar walking problems.
“As the proband’s father had similar walking problems, it was inferred that the disease was probably dominantly inherited.”
Quote in the paperNot a substantial claim- The authors state this as an assumption: The deceased family members I-2 and II-2 were affected by the disease.
- Interpretationreasoning
The c.712-2A>G variant is responsible for the SPG8 in the proband.
“Given the degree of protein structure alteration, it was highly considered that the c.712–2A>G variant was responsible for the SPG8 in the proband.”
Quote in the paperSubstantial claim- Rests on an assumption: Mutations in the WASHC5 gene can lead to SPG8.
- Probably not a substantial claim. 13
- It may state two separate claims as one. 11
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Findingnone givenThe proband was initially clinically diagnosed with spastic paraplegia.
“The proband was initially clinically diagnosed with spastic paraplegia.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataThe retention of 30 nucleotides leads to insertion of 10 aberrant amino acids (LSRGVVLTLR) at position 237 of the WASHC5 protein, resulting in an abnormally prolonged protein of 1,169 amino acids.
“The retention of 30 nucleotides leads to the insertion of 10 aberrant amino acids (LSRGVVLTLR) at position 237 of the WASHC5 protein, thus resulting in an abnormally prolonged protein (1,169 aa) (Figures 1I, K).”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Findingown dataThe self-rating anxiety scale and self-rating depression scale showed mild anxiety (SAS score 51) and severe depression (SDS score 0.75) in the proband.
“The self-rating anxiety scale (SAS) and self-rating depression scale (SDS) (Yue et al., 2020) were carried out, and the results showed mild anxiety (SAS score: 51, range 0–100) and severe depression (SDS score: 0.75, range 0–1).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Yue et al., 2020 source
It may state two separate claims as one.
Findingown dataThe c.712-2A>G variant is absent from the 1,000 Genomes Project, ExAC, and ESP6500 databases and has a frequency of 0.000004 (1/251100) in gnomAD.
“The c.712–2A>G variant was not found in the 1,000 Genomes Project (1,000G; http://www.1000genomes.org/), the Exome Aggregation Consortium (ExAC) database (http://exac.broadinstitute.org), and the NHLBI Exome Sequencing Project Exome Variant Server (ESP6500) and has a frequency of 0.000004 (1/251100) in the Genome Aggregation Database (GnomAD; http://gnomad.broadinstitule.org).”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown dataThe electroencephalogram showed mild abnormalities.
“The electroencephalogram (EEG) showed mild abnormalities (Figure 1E).”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataBrain MRI of the proband showed mild brain atrophy, and spinal cord MRI scans were normal.
“The brain magnetic resonance imaging (MRI) of the proband showed mild brain atrophy (Figure 1A). The spinal cord MRI scans were normal (Figures 1B–D).”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown dataElectromyography revealed absence of spontaneous muscle activity in the examined muscles of the proband's left lower limb.
“The electromyography results revealed the absence of spontaneous muscle activity in the examined muscles of the proband’s left lower limb.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataThe proband with the heterozygous c.712-2A>G variant showed two PCR products of 307 and 337 nucleotides, corresponding to the wild-type and mutated allele, while relatives without the variant only had a single 307-nucleotide product.
“The Sanger sequence analysis of the region encompassing exon 6 and exon 7 found that the proband with the heterozygous c.712–2A>G variant showed two PCR products of 307 nucleotides and 337 nucleotides, corresponding to the wild-type and the mutated allele, respectively.”
- Also stated in: § RNA splicing analysis · plain
“In contrast, relatives without the c.712–2A>G variant only had a single PCR product of the expected size (307 nucleotides) (Figure 1J).”
Quote in the paperSubstantial claim- Also stated in: § RNA splicing analysis · plain
Probably not a substantial claim. It may state two separate claims as one.
Study design and conductnone givenTwo groups were compared using the unpaired Student's t-test, and a p-value <0.05 was considered statistically significant.
“Two groups were compared using the unpaired Student’s t-test. A p-value <0.05 was considered statistically significant.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationSPG8 is a rare autosomal dominant HSP characterized by onset of progressive lower limb spasticity and hyperreflexia in adults, resulting in impaired gait and difficulty in walking.
“SPG8 is a rare autosomal dominant HSP characterized by onset of progressive lower limb spasticity and hyperreflexia in adults, resulting in impaired gait and difficulty in walking.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites de Bot et al., 2013 source
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationStrumpellin, encoded by WASHC5, is a key member of the WASH complex and can activate the ARP2/3 complex and interact with p97/VCP.
“Strumpellin, encoded by the WASHC5 gene, is a key member of the Wiskott–Aldrich syndrome protein and SCAR homolog (WASH) complex. Strumpellin can activate the ubiquitous actin-related protein 2/3 (ARP2/3) complex and interact with p97/VCP (Fokin et al., 2021; Song et al., 2018).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationWASH complex-mediated actin is essential for both endosomal and lysosomal networks.
“WASH complex-mediated actin is essential for both endosomal and lysosomal networks (Courtland et al., 2021; Gomez et al., 2012).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim. It may state two separate claims as one.
PremisecitationPathogenic WASHC5 mutations in strumpellin can induce defects in endosomal fission or lysosome morphology, which further leads to HSP.
“Pathogenic WASHC5 mutations in strumpellin can induce defects in endosomal fission or lysosome morphology, which further leads to HSP (Lee et al., 2020; Song et al., 2018).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationTo date, approximately 37 variants in WASHC5, including three splice mutations and one gross deletion variant, have been identified in a range of phenotypes.
“To date, approximately 37 variants in WASHC5, including three splice mutations and one gross deletion variant, have been identified in a range of phenotypes (Elliott et al., 2013; Mulroy et al., 2021; D'Amore et al., 2018; Ma et al., 2018).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Study design and conductown dataWES yielded 10.21 GB data with 98.1% coverage of the target regions and 96.0% of the target covered over ×10.
“WES yielded 10.21 GB data with 98.1% coverage of the target regions and 96.0% of the target covered over ×10.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
PremisecitationDisruption of either one of the five WASH complex subunits makes the whole complex unstable and may disturb the quantity of other WASH complex members.
“Previous studies have reported that disruption of either one of the five WASH complex subunits makes the whole complex unstable and may disturb the quantity of other WASH complex members (Jahic et al., 2015; Song et al., 2018).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationAbnormal strumpellin may lead to defects in the endosomal and lysosomal systems.
“Furthermore, the abnormal strumpellin may lead to defects in the endosomal and lysosomal systems (Gomez et al., 2012; Lee et al., 2020; Song et al., 2018).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductnone givenThe qPCR experiment was repeated more than three times.
“The experiment was repeated more than three times.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
Mutations in the WASHC5 gene can lead to SPG8.
“Mutations in the WASHC5 gene, also known as the KIAA0196 gene, can lead to SPG8 (OMIM#603563).”
“Mutations in the WASHC5 gene are associated with autosomal dominant HSP, spastic paraplegia 8 (SPG8).”
The authors state this as an assumption.
The deceased family members I-2 and II-2 were affected by the disease.
“The deceased family members (I-2 and II-2) were not examined; however, they were considered affected according to relatives.”
The paper relies on this without support.
The c.712–2A>G variant has not been published.
“Notably, the c.712–2A>G variant reported in this study has not been published; therefore, it is considered novel.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Splicing result cites the WES-filtering panel
MinorThe discussion cites Figure 1H for the aberrant transcript, but the figure legend identifies panel H as the WES filtering schematic, not a transcript result.
“RNA splicing analysis revealed that the c.712–2A>G variant gave rise to a 337-nucleotide aberrant transcript in the proband, compared with the expected size transcript (307 nucleotides) in the healthy control (Figure 1H).”
“(H) Schematic representation of the filtering strategies employed in the WES analysis.”
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Ichinose, Y., Koh, K., Fukumoto, M., Yamashiro, N., Kobayashi, F., Miwa, M., Nagasaka, T., Shindo, K., Ishiura, H., Tsuji, S., et al. (2016) · Clinical Neurology and Neurosurgery · doi:10.1016/j.clineuro.2016.02.031 · Cited by 11
Clemen, C. S., Schmidt, A., Winter, L., Canneva, F., Wittig, I., Becker, L., Coras, R., Berwanger, C., Hofmann, A., Eggers, B., et al. (2021) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12750 · Cited by 10
Determinants of age at onset in a Portuguese cohort of autosomal dominant spastic paraplegia
Rodrigues, R., Silva, R. V. D. S., Branco, M., Brandão, E., Alonso, I. D. C. M. P., Ruano, L., & Loureiro, J. L. (2019) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2019.116646 · Cited by 9
A novel KIAA0196 mutation in a Chinese patient with spastic paraplegia 8: A case report
Ma, L., Shi, Y., Chen, Z., Li, S., Qin, W., & Zhang, J. (2018) · Medicine · doi:10.1097/md.0000000000010760 · Cited by 7
Elevated hydroxycholesterols in Norwegian patients with hereditary spastic paraplegia SPG5
Prestsæter, S., Koht, J. A., Lamari, F., Tallaksen, C. M. E., Hoven, S. T. J., Vigeland, M. D., Selmer, K. K., & Rydning, S. L. (2020) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.117211 · Cited by 6
Paroxysmal, exercise-induced, diurnally fluctuating dystonia: expanding the phenotype of SPG8
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Preimplantation Genetic Testing for Spastic Paraplegia Type 3
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Sorted by citations
CCDC22 mutations that impair COMMD binding cause attenuated 3C/Ritscher-Schinzel syndrome
Singla, A., Rogers, C., Touma, M.-J., El-Najjar, Y., Colley, A., Boesch, D. J., Billadeau, D. D., Gecz, J., Chen, B., & Burstein, E. (2025) · BMC Medical Genomics · doi:10.1186/s12920-025-02168-7 · Cited by 1
WASHC3 knockout disrupts mitochondrial protein homeostasis and energy metabolism in cardiomyocytes
Kim, S. Y., Park, D.-D., Glazier, A. A., Rottbauer, W., & Just, S. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1682381
Metadata
- Authors
- Gao, S.-Y., Liu, Y.-X., Dong, Y., Fan, L.-L., Ding, Q., & Liu, L.
- Affiliations
- Central South University (CN)
- Changshu No. 2 People's Hospital (CN)
- Corresponding author
- Ding, Qi
- Liu, Lv
- Venue
- Frontiers in Genetics
- Publisher
- Frontiers Media SA
- Published
- 2023-10-31
- Volume
- 14
- Pages
- 1205052-1205052
- ISSN
- 1664-8021 (ISSN-L)
- PMC
- PMC10644772
- OpenAlex
- W4388047460
- Cited by
- 2
- References
- 31
- Citations by year
- 2026: 1 · 2025: 1
- FWCI
- 0.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82000079)
- 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 › Molecular Biology › RNA Research and Splicing
- Keywords
- hereditary spastic paraplegia, splice-altering variants, mRNA splicing, WASH complex, Wiskott-Aldrich syndrome protein, restless legs syndrome, autosomal dominant inheritance, genetic counseling
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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