Evidence map›Paper›PMID 26668131›Full record

ArticleJournal of medical genetics2016

Disruption of Golgi morphology and altered protein glycosylation in PLA2G6-associated neurodegeneration.

Mariska Davids, Megan S Kane, Miao He, Lynne A Wolfe, Xueli Li, Mohd A Raihan, Katherine R Chao, William P Bone, Cornelius F Boerkoel, William A Gahl and 1 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medical genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05440994 (Phenotypic Description of Patients With Atypical Clinical Forms of PLA2G6 Mutations), which is not on this map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
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.

NCT05440994 unknown statusnot on this mapstarted 2022, after this paper: background citation

Phenotypic Description of Patients With Atypical Clinical Forms of PLA2G6 Mutations

TypeobservationalSponsorUniversity Hospital, Clermont-FerrandRan2022 to 2022Enrolled20ConditionsNeuroaxonal Dystrophy, Atypical
3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Increased Transferrin Sialylation Predicts Phenoconversion in Isolated REM Sleep Behavior Disorder.Movement disorders : official journal of the Movement Disorder Society · 2022
    Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. ALG9-CDG: New clinical case and review of the literature.Molecular genetics and metabolism reports · 2017
    Article
  13. Article
  14. Article
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

11 authors.

Mariska DavidsNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland, USA Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, Maryland, USA.
Megan S KaneNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland, USA Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, Maryland, USA.
Miao HeDepartment of Pathology and Laboratory of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA The Michael J Palmieri Metabolic Laboratory, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Lynne A WolfeNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland, USA Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, Maryland, USA.
Xueli LiDepartment of Pathology and Laboratory of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA The Michael J Palmieri Metabolic Laboratory, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Mohd A RaihanDepartment of Pathology and Laboratory of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA The Michael J Palmieri Metabolic Laboratory, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Katherine R ChaoNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland, USA Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, Maryland, USA.
William P BoneNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland, USA Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, Maryland, USA.
Cornelius F BoerkoelNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland, USA Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, Maryland, USA.
William A GahlNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland, USA Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, Maryland, USA.
Camilo ToroNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland, USA Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, Maryland, USA.

Funding

Human Biochemical GeneticsZIAHG000215 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM · 2009 to 2025
$72.6M
Intramural NIH HHS Z99 HG999999
6 · The paper itself

Abstract

backgroundMutations in PLA2G6, which encodes the calcium-independent phospholipase A2 group VI, cause neurodegeneration and diffuse cortical Lewy body formation by a yet undefined mechanism. We assessed whether altered protein glycosylation due to abnormal Golgi morphology might be a factor in the pathology of this disease.

methodsThree patients presented with PLA2G6-associated neurodegeneration (PLAN); two had infantile neuroaxonal dystrophy (INAD) and one had adult-onset dystonia-parkinsonism. We analysed protein N-linked and O-linked glycosylation in cerebrospinal fluid, plasma, urine, and cultured skin fibroblasts using high performance liquid chromatography (HPLC) and matrix-assisted laser desorption ionization--time of flight/mass spectrometry (MALDI-TOF/MS). We also assessed sialylation and Golgi morphology in cultured fibroblasts by immunofluorescence and performed rescue experiments using a lentiviral vector.

resultsThe patients with INAD had PLA2G6 mutations NM_003560.2: c.[950G>T];[426-1077dup] and c.[1799G>A];[2221C>T] and the patient with dystonia-parkinsonism had PLA2G6 mutations NM_003560.2: c.[609G>A];[2222G>A]. All three patients had altered Golgi morphology and abnormalities of protein O-linked glycosylation and sialylation in cultured fibroblasts that were rescued by lentiviral overexpression of wild type PLA2G6.

conclusionsOur findings add altered Golgi morphology, O-linked glycosylation and sialylation defects to the phenotypical spectrum of PLAN; these pathways are essential for correct processing and distribution of proteins. Lewy body and Tau pathology, two neuropathological features of PLAN, could emerge from these defects. Therefore, Golgi morphology, O-linked glycosylation and sialylation may play a role in the pathogenesis of PLAN and perhaps other neurodegenerative disorders.

Indexed as

AdultCells, CulturedDystonic DisordersFemaleFibroblastsGlycosylationGolgi ApparatusGroup VI Phospholipases A2HumansInfantMaleMutationNeuroaxonal DystrophiesNeurodegenerative DiseasesParkinsonian DisordersSialyltransferasesGroup VI Phospholipases A2PLA2G6 protein, humanSialyltransferasesCell biologyMolecular geneticsNeuromuscular disease

Identifiers

PMID26668131
PMCPMC5535303

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Registered trials

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.