Evidence map›Paper›PMID 24863970›Full record

ArticleMolecular genetics and metabolism2014

Three rare diseases in one Sib pair: RAI1, PCK1, GRIN2B mutations associated with Smith-Magenis Syndrome, cytosolic PEPCK deficiency and NMDA receptor glutamate insensitivity.

David R Adams, Hongjie Yuan, Todd Holyoak, Katrina H Arajs, Parvin Hakimi, Thomas C Markello, Lynne A Wolfe, Thierry Vilboux, Barbara K Burton, Karin Fuentes Fajardo and 15 more

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

Article in Molecular genetics and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

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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

25 authors at 10 institutions in 3 countries.

David R AdamsUndiagnosed Diseases Program, Office of the Director, National Institutes of Health, Bethesda, MD, USA; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA. Electronic address: david.adams@nih.gov.
Hongjie YuanDepartment of Pharmacology, Emory University School of Medicine, Rollins Research Center, Atlanta, GA, USA.
Todd HolyoakDepartment of Biology, University of Waterloo, Waterloo, ON, Canada.
Katrina H ArajsDepartment of Biology, University of Waterloo, Waterloo, ON, Canada.
Parvin HakimiDepartment of Biochemistry, Case Western Reserve University, USA; Department of Pediatrics, Case Western Reserve University, USA.
Thomas C MarkelloUndiagnosed Diseases Program, Office of the Director, National Institutes of Health, Bethesda, MD, USA.
Lynne A WolfeUndiagnosed Diseases Program, Office of the Director, National Institutes of Health, Bethesda, MD, USA.
Thierry VilbouxMedical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA.
Barbara K BurtonAnn and Robert H. Lurie Children's Hospital, Northwestern University, Chicago, IL, USA; Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Karin Fuentes FajardoUndiagnosed Diseases Program, Office of the Director, National Institutes of Health, Bethesda, MD, USA.
George GrahameCenter for Inherited Disorders of Energy Metabolism, University Hospitals Case Medical Center, Cleveland, OH, USA.
Conisha HollomanUniversity of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Murat SincanUndiagnosed Diseases Program, Office of the Director, National Institutes of Health, Bethesda, MD, USA.
Ann C M SmithUndiagnosed Diseases Program, Office of the Director, National Institutes of Health, Bethesda, MD, USA.
Gordon A WellsDepartment of Chemistry, Emory University, Atlanta, GA, USA; Department of Biochemistry, University of Stellenbosch, South Africa.
Yan HuangUndiagnosed Diseases Program, Office of the Director, National Institutes of Health, Bethesda, MD, USA.
Hugo VegaUndiagnosed Diseases Program, Office of the Director, National Institutes of Health, Bethesda, MD, USA.
James P SnyderDepartment of Chemistry, Emory University, Atlanta, GA, USA.
Gretchen A GolasUndiagnosed Diseases Program, Office of the Director, National Institutes of Health, Bethesda, MD, USA.
Cynthia J TifftUndiagnosed Diseases Program, Office of the Director, National Institutes of Health, Bethesda, MD, USA.
Cornelius F BoerkoelUndiagnosed Diseases Program, Office of the Director, National Institutes of Health, Bethesda, MD, USA.
Richard W HansonDepartment of Biochemistry, Case Western Reserve University, USA.
Stephen F TraynelisDepartment of Pharmacology, Emory University School of Medicine, Rollins Research Center, Atlanta, GA, USA.
Douglas S KerrDepartment of Biochemistry, Case Western Reserve University, USA; Department of Pediatrics, Case Western Reserve University, USA; Center for Inherited Disorders of Energy Metabolism, University Hospitals Case Medical Center, Cleveland, OH, USA.
William A GahlUndiagnosed Diseases Program, Office of the Director, National Institutes of Health, Bethesda, MD, USA; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA.
Office of the Director · USNational Institutes of Health · USCase Western Reserve University · USEmory University · USUniversity of Waterloo · CALurie Children's Hospital · USNational Human Genome Research Institute · USStellenbosch University · ZAUniversity Hospitals Case Medical Center · USUniversity of Rochester · US

Funding

Human Biochemical GeneticsZIAHG000215 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM · 2009 to 2025
$72.6M
TRAFFICKING OF THE PLASMA MEMBRANE CA2+-ATPASE TO RAFTSP20RR017708 · NCRR · UNIVERSITY OF KANSAS LAWRENCE · PI FISCHER, CHRISTOPHER JAMES · 2002 to 2011
$20.1M
Control of Glutamate Receptor FunctionR01NS036654 · NINDS · EMORY UNIVERSITY · PI TRAYNELIS, STEPHEN F · 1998 to 2018
$3.7M
Control of glutamate receptor functionR37NS036654 · NINDS · EMORY UNIVERSITY · PI TRAYNELIS, STEPHEN F · 2007 to 2013
$2.4M
Intramural NIH HHS Z99 HG999999NCRR NIH HHS P20 RR017708NCRR NIH HHS P20 RR17708NINDS NIH HHS NS036654NINDS NIH HHS R01 NS036654NINDS NIH HHS R37 NS036654PHS HHS HSN268201300162P
6 · The paper itself

Abstract

The National Institutes of Health Undiagnosed Diseases Program evaluates patients for whom no diagnosis has been discovered despite a comprehensive diagnostic workup. Failure to diagnose a condition may arise from the mutation of genes previously unassociated with disease. However, we hypothesized that this could also co-occur with multiple genetic disorders. Demonstrating a complex syndrome caused by multiple disorders, we report two siblings manifesting both similar and disparate signs and symptoms. They shared a history of episodes of hypoglycemia and lactic acidosis, but had differing exam findings and developmental courses. Clinical acumen and exome sequencing combined with biochemical and functional studies identified three genetic conditions. One sibling had Smith-Magenis Syndrome and a nonsense mutation in the RAI1 gene. The second sibling had a de novo mutation in GRIN2B, which resulted in markedly reduced glutamate potency of the encoded receptor. Both siblings had a protein-destabilizing homozygous mutation in PCK1, which encodes the cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK-C). In summary, we present the first clinically-characterized mutation of PCK1 and demonstrate that complex medical disorders can represent the co-occurrence of multiple diseases.

Indexed as

Amino Acid SequenceBase SequenceChildChild, PreschoolDNA Mutational AnalysisFemaleGenetic Association StudiesHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsMolecular Sequence DataMutation, MissensePhosphoenolpyruvate Carboxykinase (ATP)Phosphoenolpyruvate Carboxykinase (GTP)Polymorphism, Single NucleotideReceptors, N-Methyl-D-AspartateIntracellular Signaling Peptides and ProteinsNR2B NMDA receptorPCK1 protein, humanPCK2 protein, humanPhosphoenolpyruvate Carboxykinase (ATP)Phosphoenolpyruvate Carboxykinase (GTP)RAI1 protein, humanReceptors, N-Methyl-D-AspartateTrans-ActivatorsTranscription FactorsDevelopmental delayDysmorphismHypoglycemiaLactic acidemiaMultiple genetic disordersProtein structure-function

Identifiers

PMID24863970
PMCPMC4219933
OpenAlexW2015656754

What OpenQuestion holds

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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.