Evidence map›Paper›PMID 32220290›Full record

ArticleAmerican journal of human genetics2020

Bi-allelic Variants in the GPI Transamidase Subunit PIGK Cause a Neurodevelopmental Syndrome with Hypotonia, Cerebellar Atrophy, and Epilepsy.

Thi Tuyet Mai Nguyen, Yoshiko Murakami, Sabrina Mobilio, Marcello Niceta, Giuseppe Zampino, Christophe Philippe, Sébastien Moutton, Maha S Zaki, Kiely N James, Damir Musaev and 28 more

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In one paragraph

Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 6% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Molecular Insights into Fungal Glycosylphosphatidylinositol Transamidase Complex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  11. Observational
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  18. A Novel HomozygousGenes · 2023
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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

38 authors at 16 institutions in 7 countries.

Thi Tuyet Mai NguyenCHU-Sainte Justine Research Center, University of Montreal, Montreal, QC, Canada, H3T1C5.
Yoshiko MurakamiResearch Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Sabrina MobilioDivision of Medical Genetics, Northwell Health, Manhasset, NY 11030, USA.
Marcello NicetaGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Giuseppe ZampinoCenter for Rare Disease and Congenital Defects, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Christophe PhilippeUF Innovation en diagnostic génomique des maladies rares, CHU Dijon Bourgogne, and INSERM UMR1231 GAD, F-21000, Dijon, France.
Sébastien MouttonReference Center for Developmental Anomalies, Department of Medical Genetics, Dijon University Hospital, Dijon, France.
Maha S ZakiClinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo 12311, Egypt.
Kiely N JamesLaboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA 92123, USA.
Damir MusaevLaboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA 92123, USA.
Weiyi MuInstitute of Genetic Medicine, Johns Hopkins University, Baltimore MD, USA.
Kristin BarananoDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, 21287 USA.
Jessica R NanceDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, 21287 USA.
Jill A RosenfeldBaylor College of Medicine, Houston, TX 77030, USA.
Nancy BravermanDepartment of Human Genetics, McGill University and Montreal Children's Hospital, Montreal, QC, Canada, H4A 3J1.
Andrea CiolfiGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Francisca MillanGeneDx, Gaithersburg, MD 20877, USA.
Richard E PersonGeneDx, Gaithersburg, MD 20877, USA.
Ange-Line BruelUF Innovation en diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon, France.
Christel Thauvin-RobinetCentre de référence maladies rares-Déficiences Intellectuelles de causes rares, Centre de génétique, Hôpital d'Enfants, UF Innovation en diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon.
Athina VerveriClinical Genetic Service, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK.
Catherine DeVileDepartment of Neurology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK.
Alison MaleClinical Genetic Service, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK.
Stephanie EfthymiouDepartment of Neuromuscular Disorders, UCL Institute of Neurology, London WC1N 3BG, UK.
Reza MaroofianDepartment of Neuromuscular Disorders, UCL Institute of Neurology, London WC1N 3BG, UK.
Henry HouldenDepartment of Neuromuscular Disorders, UCL Institute of Neurology, London WC1N 3BG, UK.
Shazia MaqboolDevelopment and Behavioural Pediatrics Department, Institute of Child Health and The Children Hospital, Lahore, Pakistan.
Fatima RahmanDevelopment and Behavioural Pediatrics Department, Institute of Child Health and The Children Hospital, Lahore, Pakistan.
Nissan V BaratangCHU-Sainte Justine Research Center, University of Montreal, Montreal, QC, Canada, H3T1C5.
Justine RousseauCHU-Sainte Justine Research Center, University of Montreal, Montreal, QC, Canada, H3T1C5.
Anik St-DenisCHU-Sainte Justine Research Center, University of Montreal, Montreal, QC, Canada, H3T1C5.
Matthew J ElrickDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, 21287 USA.
Irina AnselmDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Lance H RodanDivision of Genetics and Genomics and Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Marco TartagliaGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Joseph GleesonLaboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA 92123, USA.
Taroh KinoshitaResearch Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Philippe M CampeauCHU-Sainte Justine Research Center, University of Montreal, Montreal, QC, Canada, H3T1C5; Department of Pediatrics, University of Montreal, Montreal, QC, Canada, H3T1C5. Electronic address: p.campeau@umontreal.ca.
Centre Hospitalier Universitaire Sainte-Justine · CAJohns Hopkins University · USBambino Gesù Children's Hospital · ITChildren’s Institute · USGreat Ormond Street Hospital for Children NHS Foundation Trust · GBUniversity College London · GBBoston Children's Hospital · USThe University of Osaka · JPBaylor College of Medicine · USHôpital d'Enfants · FRInserm · FRMaison des Sciences sociales et des Humanités de Dijon · FRMontreal Children's Hospital · CANational Research Centre · EGNorthwell Health · USUniversità Cattolica del Sacro Cuore · IT

Funding

Cancer Research UKCIHRMedical Research CouncilWellcome TrustWellcome Trust WT093205Wellcome Trust WT104033AIA
6 · The paper itself

Abstract

Glycosylphosphatidylinositol (GPI)-anchored proteins are critical for embryogenesis, neurogenesis, and cell signaling. Variants in several genes participating in GPI biosynthesis and processing lead to decreased cell surface presence of GPI-anchored proteins (GPI-APs) and cause inherited GPI deficiency disorders (IGDs). In this report, we describe 12 individuals from nine unrelated families with 10 different bi-allelic PIGK variants. PIGK encodes a component of the GPI transamidase complex, which attaches the GPI anchor to proteins. Clinical features found in most individuals include global developmental delay and/or intellectual disability, hypotonia, cerebellar ataxia, cerebellar atrophy, and facial dysmorphisms. The majority of the individuals have epilepsy. Two individuals have slightly decreased levels of serum alkaline phosphatase, while eight do not. Flow cytometric analysis of blood and fibroblasts from affected individuals showed decreased cell surface presence of GPI-APs. The overexpression of wild-type (WT) PIGK in fibroblasts rescued the levels of cell surface GPI-APs. In a knockout cell line, transfection with WT PIGK also rescued the GPI-AP levels, but transfection with the two tested mutant variants did not. Our study not only expands the clinical and known genetic spectrum of IGDs, but it also expands the genetic differential diagnosis for cerebellar atrophy. Given the fact that cerebellar atrophy is seen in other IGDs, flow cytometry for GPI-APs should be considered in the work-ups of individuals presenting this feature.

Indexed as

Abnormalities, MultipleAcyltransferasesAllelesCell Adhesion MoleculesCerebellar DiseasesEpilepsyFemaleGenetic VariationHumansIntellectual DisabilityMaleMuscle HypotoniaNervous System MalformationsNeurodevelopmental DisordersPedigreeSyndromeAcyltransferasesCell Adhesion MoleculesCOOH-terminal signal transamidasePIGK protein, humanglycosylphosphatidylinositol (GPI)GPI8inherited GPI deficiency disorders (IGDs)PIGKtransamidase

Identifiers

PMID32220290
PMCPMC7118585
OpenAlexW3013173075

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.