Evidence map›Paper›PMID 24999486›Full record

ArticleAnnals of clinical and translational neurology2014

Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11.

Benoît Renvoisé, Jaerak Chang, Rajat Singh, Sayuri Yonekawa, Edmond J FitzGibbon, Ami Mankodi, Adeline Vanderver, Alice Schindler, Camilo Toro, William A Gahl and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of clinical and translational neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.

  1. Frontiers in neuroscience · 2019
    Pooled it
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  17. Movement disorders in hereditary spastic paraplegias.Arquivos de neuro-psiquiatria · 2023
    Review
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  19. Article
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17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 6 institutions in 2 countries.

Benoît RenvoiséNeurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Jaerak ChangNeurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Rajat SinghNeurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Sayuri YonekawaResearch Institute, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
Edmond J FitzGibbonLaboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Ami MankodiNeurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Adeline VanderverDepartment of Neurology, Children's National Medical Center, Washington, DC, USA.
Alice SchindlerNeurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Camilo ToroOffice of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA ; NIH Undiagnosed Diseases Program, National Institutes of Health, Office of Rare Diseases Research and National Human Genome Research Institute, Bethesda, MD, USA.
William A GahlOffice of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA ; NIH Undiagnosed Diseases Program, National Institutes of Health, Office of Rare Diseases Research and National Human Genome Research Institute, Bethesda, MD, USA.
Don J MahuranResearch Institute, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
Craig BlackstoneNeurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Tyler Mark PiersonNeurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA ; NIH Undiagnosed Diseases Program, National Institutes of Health, Office of Rare Diseases Research and National Human Genome Research Institute, Bethesda, MD, USA ; Departments of Pediatrics and Neurology, and the Regenerative Medicine Institute, Cedars- Sinai Medical Center, Los Angeles, CA, USA.
National Institute of Neurological Disorders and Stroke · USNational Institutes of Health · USHospital for Sick Children · CAChildren's National · USNational Eye Institute · USNational Human Genome Research Institute · US

Funding

Human Biochemical GeneticsZIAHG000215 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM · 2009 to 2025
$72.6M
Molecular Pathogenesis Of Hereditary Spastic ParaplegiasZIANS002992 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI BLACKSTONE, CRAIG · 2009 to 2021
$20.6M
Studies of Hereditary Neurological Disease: Disease MechanismsZIANS003038 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI FISCHBECK, KENNETH · 2009 to 2023
$19.5M
Endocytic Mechanisms in the Hereditary Spastic ParaplegiasZIANS003128 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI BLACKSTONE, CRAIG · 2011 to 2021
$13.1M
Hereditary Muscle Disease UnitZIANS003131 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI MANKODI, AMI · 2012 to 2023
$11.7M
Neuro-ophthalmic Mechanisms Of DiseaseZIAEY000388 · NEI · NATIONAL EYE INSTITUTE · PI FITZGIBBON, EDMOND J · 2009 to 2023
$5.1M
Molecular Pathology Of Hereditary Neurological DisordersZ01NS002992 · NINDS · NEUROLOGICAL DISORDERS AND STROKE · PI BLACKSTONE, CRAIG D · 2002 to 2008
$3.1M
Intramural NIH HHS Z01 NS002992
6 · The paper itself

Abstract

objectiveHereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to early-onset parkinsonism.

methodsWe describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes.

resultsFibroblasts prepared from patients with SPG15 have selective enlargement of LAMP1-positive structures, and they consistently exhibited abnormal lysosomal storage by electron microscopy. A similar enlargement of LAMP1-positive structures was also observed in cells from multiple SPG11 patients, though prominent abnormal lysosomal storage was not evident. The stabilities of the SPG15 protein spastizin/ZFYVE26 and the SPG11 protein spatacsin were interdependent.

interpretationEmerging studies implicating these two proteins in interactions with the late endosomal/lysosomal adaptor protein complex AP-5 are consistent with shared abnormalities in lysosomes, supporting a converging mechanism for these two disorders. Recent work with

Identifiers

PMID24999486
PMCPMC4078876
OpenAlexW2008201415

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.