Evidence map›Paper›PMID 24651605›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2014

Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway.

Gregory M Enns, Vandana Shashi, Matthew Bainbridge, Michael J Gambello, Farah R Zahir, Thomas Bast, Rebecca Crimian, Kelly Schoch, Julia Platt, Rachel Cox and 25 more

Erratum issuedOpen access · greenAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 126 papers.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed
9.6field-weighted citation impact, top 1% 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

126 citing papers in PubMed, 236 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

66 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors at 13 institutions in 4 countries.

Gregory M EnnsDepartment of Pediatrics, Division of Medical Genetics, Lucile Packard Children's Hospital, Stanford University, Stanford, California, USA.
Vandana ShashiDepartment of Pediatrics, Division of Medical Genetics, Duke University, Durham, North Carolina, USA.
Matthew BainbridgeDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Michael J GambelloDepartment of Human Genetics, Division of Medical Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Farah R ZahirDepartment of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Thomas BastEpilepsy Centre Kork, Kehl, Germany.
Rebecca CrimianDepartment of Pediatrics, Division of Medical Genetics, Duke University, Durham, North Carolina, USA.
Kelly SchochDepartment of Pediatrics, Division of Medical Genetics, Duke University, Durham, North Carolina, USA.
Julia PlattDepartment of Pediatrics, Division of Medical Genetics, Lucile Packard Children's Hospital, Stanford University, Stanford, California, USA.
Rachel CoxDepartment of Pediatrics, Division of Medical Genetics, Lucile Packard Children's Hospital, Stanford University, Stanford, California, USA.
Jonathan A BernsteinDepartment of Pediatrics, Division of Medical Genetics, Lucile Packard Children's Hospital, Stanford University, Stanford, California, USA.
Mena ScavinaDivision of Pediatric Neurology, Department of Pediatrics, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware, USA.
Rhonda S WalterDivision of Developmental Medicine, Department of Pediatrics, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware, USA.
Audrey BibbDepartment of Human Genetics, Division of Medical Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Melanie JonesDepartment of Human Genetics, Division of Medical Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Madhuri HegdeDepartment of Human Genetics, Division of Medical Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Brett H GrahamDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Anna C NeedDepartment of Medicine, Imperial College, London, UK.
Angelica OviedoDepartment of Pathology and Laboratory Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Christian P Schaaf1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA [2] Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, USA.
Sean BoyleDepartment of Genetics, Stanford University, Stanford, California, USA.
Atul J ButteDepartment of Genetics, Stanford University, Stanford, California, USA.
Rui ChenDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Rong ChenDepartment of Genetics, Stanford University, Stanford, California, USA.
Michael J ClarkDepartment of Genetics, Stanford University, Stanford, California, USA.
Rajini HaraksinghDepartment of Genetics, Stanford University, Stanford, California, USA.
FORGE Canada Consortium
Tina M CowanDepartment of Pathology, Stanford University, Stanford, California, USA.
Ping HeSanford-Burnham Medical Research Institute, La Jolla, California, USA.
Sylvie LangloisDepartment of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Huda Y Zoghbi1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA [2] Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, USA [3] Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, USA.
Michael SnyderDepartment of Genetics, Stanford University, Stanford, California, USA.
Richard A Gibbs1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA [2] Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
Hudson H FreezeSanford-Burnham Medical Research Institute, La Jolla, California, USA.
David B Goldstein1] Center for Human Genome Variation and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA [2] Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.
Stanford University · USBaylor College of Medicine · USEmory University · USLucile Packard Children's Hospital · USDuke Medical Center · USAlfred I. duPont Hospital for Children · USSanford Burnham Prebys Medical Discovery Institute · USUniversity of British Columbia · CADalhousie University · CADiakonie Kork · DEDuke University · USImperial College London · GBTexas Medical Center · US

Funding

The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3M
INSTITUTIONAL TRAINING GRANT IN GENOME SCIENCET32HG000044 · NHGRI · STANFORD UNIVERSITY · PI MICHAEL P. SNYDER · 1995 to 2026
$32.2M
Steps towards a paternal gene activation therapy for Angelman syndromeU54HD083092 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI NELSON, DAVID LOREN, NEUL, JEFFREY L · 2014 to 2019
$7.8M
CIHRNHGRI NIH HHS T32 HG000044NHGRI NIH HHS U54 HG003273NHGRI NIH HHS U54-HG003273NICHD NIH HHS U54 HD083092
6 · The paper itself

Abstract

purposeThe endoplasmic reticulum-associated degradation pathway is responsible for the translocation of misfolded proteins across the endoplasmic reticulum membrane into the cytosol for subsequent degradation by the proteasome. To define the phenotype associated with a novel inherited disorder of cytosolic endoplasmic reticulum-associated degradation pathway dysfunction, we studied a series of eight patients with deficiency of N-glycanase 1.

methodsWhole-genome, whole-exome, or standard Sanger sequencing techniques were employed. Retrospective chart reviews were performed in order to obtain clinical data.

resultsAll patients had global developmental delay, a movement disorder, and hypotonia. Other common findings included hypolacrima or alacrima (7/8), elevated liver transaminases (6/7), microcephaly (6/8), diminished reflexes (6/8), hepatocyte cytoplasmic storage material or vacuolization (5/6), and seizures (4/8). The nonsense mutation c.1201A>T (p.R401X) was the most common deleterious allele.

conclusionNGLY1 deficiency is a novel autosomal recessive disorder of the endoplasmic reticulum-associated degradation pathway associated with neurological dysfunction, abnormal tear production, and liver disease. The majority of patients detected to date carry a specific nonsense mutation that appears to be associated with severe disease. The phenotypic spectrum is likely to enlarge as cases with a broader range of mutations are detected.

Indexed as

MutationAbnormalities, MultipleAdolescentChild, PreschoolDevelopmental DisabilitiesEndoplasmic Reticulum-Associated DegradationExomeFamily HealthFatal OutcomeFemaleGenome-Wide Association StudyHumansInfantMaleMicrocephalyMovement DisordersPeptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase

Identifiers

PMID24651605
PMCPMC4243708
OpenAlexW1987330222

What OpenQuestion holds

Textmetadata
LicenceTDM
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.