Evidence map›Paper›PMID 34113002›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021

PIGG variant pathogenicity assessment reveals characteristic features within 19 families.

Camille Tremblay-Laganière, Reza Maroofian, Thi Tuyet Mai Nguyen, Ehsan Ghayoor Karimiani, Salman Kirmani, Fizza Akbar, Shahnaz Ibrahim, Bushra Afroze, Mohammad Doosti, Farah Ashrafzadeh and 41 more

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Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

6 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
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  4. MED27, SLC6A7, and MPPE1 Variants in a Complex Neurodevelopmental Disorder with Severe Dystonia.Movement disorders : official journal of the Movement Disorder Society · 2022
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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

51 authors at 20 institutions in 11 countries.

Camille Tremblay-LaganièreDepartment of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine and University of Montreal, Montreal, QC, Canada.
Reza MaroofianDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.
Thi Tuyet Mai NguyenDepartment of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine and University of Montreal, Montreal, QC, Canada.
Ehsan Ghayoor KarimianiGenetics Research Centre, Molecular and Clinical Sciences Institute, St. George's Hospital, University of London, London, UK.
Salman KirmaniDepartment of Pediatrics & Child Health, Aga Khan University, Karachi, Pakistan.
Fizza AkbarDepartment of Pediatrics & Child Health, Aga Khan University, Karachi, Pakistan.
Shahnaz IbrahimDepartment of Pediatrics & Child Health, Aga Khan University, Karachi, Pakistan.
Bushra AfrozeDepartment of Pediatrics & Child Health, Aga Khan University, Karachi, Pakistan.
Mohammad DoostiNext Generation Genetic Polyclinic, Mashhad, Iran.
Farah AshrafzadehDepartment of Pediatric Neurology, Mashhad University of Medical Sciences, Mashhad, Iran.
Meisam BabaeiDepartment of Pediatrics, North Khorasan University of Medical Sciences, Bojnurd, Iran.
Stephanie EfthymiouDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.
Marilena ChristoforouDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.
Tipu SultanDepartment of Pediatric Neurology, Institute of Child Health, The Children's Hospital Lahore, Lahore, Pakistan.
Roger L LaddaDepartment of Pediatrics, Milton S Hershey Medical Centre, Hershey, PA, USA.
Heather M McLaughlinInvitae Corporation, San Francisco, CA, USA.
Rebecca TrutyInvitae Corporation, San Francisco, CA, USA.
Sonal MahidaDivision of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA.
Julie S CohenDivision of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA.
Kristin BarananoDivision of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA.
Fatima Y IsmailDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Millan S PatelDepartment of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Anna LehmanDepartment of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Andrew C EdmondsonDivision of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Amanda NagyDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Melissa A WalkerDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Saadet Mercimek-AndrewsDivision of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON, Canada.
Yuta MakiDepartment of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan.
Rani SachdevSydney Children's Hospital, Centre for Clinical Genetics, Sydney Children's Hospital, High St, Randwick, UK.
Rebecca MacintoshSydney Children's Hospital, Centre for Clinical Genetics, Sydney Children's Hospital, High St, Randwick, UK.
Elizabeth E PalmerSydney Children's Hospital, Centre for Clinical Genetics, Sydney Children's Hospital, High St, Randwick, UK.
Grazia M S ManciniDepartment of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands, CA, Rotterdam, The Netherlands.
Tahsin Stefan BarakatDepartment of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands, CA, Rotterdam, The Netherlands.
Robert SteinfeldDepartment of Pediatric Neurology, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
Christina T RüschDepartment of Pediatric Neurology, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
Georg M StettnerDepartment of Pediatric Neurology, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
Matias WagnerInstitute of Human Genetics, School of Medicine, Technical University Munich, Munich, Germany.
Saskia B WortmannUniversity Children's Hospital, Paracelsus Medical School, Salzburg, Austria.
Usha KiniOxford Centre for Genomic Medicine, Oxford University Hospitals NHS Trust, Oxford, UK.
Angela F BradyNorth West Thames Regional Genetics Service, London North West University Healthcare NHS Trust, Northwick Park Hospital, Harrow, UK.
Karen L StalsExeter Genomics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
Naila IsmayilovaDepartment of Paediatric Neurology, Chelsea and Westminster Hospital, London, UK.
Sian EllardExeter Genomics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
Danilo BernardoUniversity of California San Francisco, Clinical Neurology, San Francisco, CA, UK.
Kimberly NugentDepartment of Pediatrics, Baylor College of Medicine, The Children's Hospital of San Antonio, San Antonio, TX, USA.
Scott D McLeanDepartment of Pediatrics, Baylor College of Medicine, The Children's Hospital of San Antonio, San Antonio, TX, USA.
Stylianos E AntonarakisDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Henry HouldenDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.
Taroh KinoshitaYabumoto Department of Intractable Disease Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Philippe M CampeauDepartment of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine and University of Montreal, Montreal, QC, Canada. p.campeau@umontreal.ca.ORCID 0000-0001-9713-7107
Yoshiko MurakamiYabumoto Department of Intractable Disease Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan. yoshiko@biken.osaka-u.ac.jp.
Aga Khan University · PKNational Hospital for Neurology and Neurosurgery · GBBirmingham Children's Hospital · GBCentre Hospitalier Universitaire Sainte-Justine · CAKennedy Krieger Institute · USUniversity of Zurich · CHBaylor College of Medicine · USErasmus MC · NLInvitae (United States) · USMassachusetts General Hospital · USOsaka International University · JPUniversity of British Columbia · CAAlberta Health Services · CAChelsea and Westminster Hospital · GBChildren's Hospital of Philadelphia · USHelmholtz Zentrum München · DEJohns Hopkins University · USLondon North West Healthcare NHS Trust · GBMashhad University of Medical Sciences · IRNorth Khorasan University of Medical Sciences · IR

Funding

MEDICAL GENETICS RESEARCH TRAINING GRANTT32GM008638 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Rebecca Ganetzky · 1997 to 2026
$8.7M
CIHRNIGMS NIH HHS T32 GM008638Wellcome Trust
6 · The paper itself

Abstract

purposePhosphatidylinositol Glycan Anchor Biosynthesis, class G (PIGG) is an ethanolamine phosphate transferase catalyzing the modification of glycosylphosphatidylinositol (GPI). GPI serves as an anchor on the cell membrane for surface proteins called GPI-anchored proteins (GPI-APs). Pathogenic variants in genes involved in the biosynthesis of GPI cause inherited GPI deficiency (IGD), which still needs to be further characterized.

methodsWe describe 22 individuals from 19 unrelated families with biallelic variants in PIGG. We analyzed GPI-AP surface levels on granulocytes and fibroblasts for three and two individuals, respectively. We demonstrated enzymatic activity defects for PIGG variants in vitro in a PIGG/PIGO double knockout system.

resultsPhenotypic analysis of reported individuals reveals shared PIGG deficiency-associated features. All tested GPI-APs were unchanged on granulocytes whereas CD73 level in fibroblasts was decreased. In addition to classic IGD symptoms such as hypotonia, intellectual disability/developmental delay (ID/DD), and seizures, individuals with PIGG variants of null or severely decreased activity showed cerebellar atrophy, various neurological manifestations, and mitochondrial dysfunction, a feature increasingly recognized in IGDs. Individuals with mildly decreased activity showed autism spectrum disorder.

conclusionThis in vitro system is a useful method to validate the pathogenicity of variants in PIGG and to study PIGG physiological functions.

Indexed as

Autism Spectrum DisorderIntellectual DisabilityHumansMembrane ProteinsPedigreePhosphotransferases (Alcohol Group Acceptor)SeizuresVirulenceMembrane ProteinsPhosphotransferases (Alcohol Group Acceptor)PIGG protein, humanPIGO protein, human

Identifiers

PMID34113002
PMCPMC9900493
OpenAlexW3167623127

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