Evidence map›Paper›PMID 32418222›Full record

ArticleJournal of inherited metabolic disease2020

Novel defect in phosphatidylinositol 4-kinase type 2-alpha (PI4K2A) at the membrane-enzyme interface is associated with metabolic cutis laxa.

Miski Mohamed, Thatjana Gardeitchik, Shanti Balasubramaniam, Sergio Guerrero-Castillo, Daisy Dalloyaux, Sanne van Kraaij, Hanka Venselaar, Alexander Hoischen, Zsolt Urban, Ulrich Brandt and 11 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of inherited metabolic disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.7field-weighted citation impact, top 36% 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

9 citing papers in PubMed, 10 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

21 authors at 9 institutions in 6 countries.

Miski MohamedDepartment of Paediatrics, Radboud University Medical Center, Nijmegen, The Netherlands.ORCID 0000-0003-1636-1292
Thatjana GardeitchikDepartment of Paediatrics, Radboud University Medical Center, Nijmegen, The Netherlands.
Shanti BalasubramaniamClinical Genetic Department, Hospital Kuala Lumpur, Jalan Pahang, Kuala Lumpur, Malaysia.
Sergio Guerrero-CastilloRadboud Center for Mitochondrial Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Daisy DalloyauxDepartment of Paediatrics, Radboud University Medical Center, Nijmegen, The Netherlands.
Sanne van KraaijTranslational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Hanka VenselaarCenter of Molecular and Biomolecular Informatics, Radboud University Medical Center, Nijmegen, The Netherlands.
Alexander HoischenDepartment of Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Zsolt UrbanDepartment of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Ulrich BrandtRadboud Center for Mitochondrial Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Raya Al-ShawiWolfson Drug Discovery Unit, Division of Medicine, Royal Free Campus, University College London, London, UK.
J Paul SimonsWolfson Drug Discovery Unit, Division of Medicine, Royal Free Campus, University College London, London, UK.
Michele FrisonWolfson Drug Discovery Unit, Division of Medicine, Royal Free Campus, University College London, London, UK.
Lock-Hock NguClinical Genetic Department, Hospital Kuala Lumpur, Jalan Pahang, Kuala Lumpur, Malaysia.
Bert CallewaertCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Hans SpelbrinkDepartment of Paediatrics, Radboud University Medical Center, Nijmegen, The Netherlands.
Wouter W KallemeijnDepartment of Medical Biochemistry, Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
Johannes M F G AertsDepartment of Medical Biochemistry, Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
Mark G WaughLipid and Membrane Biology Group, Institute for Liver & Digestive Health, University College London, London, UK.
Eva MoravaHaywards Genetics Center, Tulane University, New Orleans, Louisiana, USA.
Ron A WeversTranslational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Radboud University Nijmegen · NLWolfson Foundation · GBLeiden University · NLGhent University Hospital · BEHospital Kuala Lumpur · MYThe University of Sydney · AUTulane University · USUniversity College London · GBUniversity of Pittsburgh · US

Funding

GENETICS OF EXTRACELLULAR MATRIX IN HEALTH AND DISEASER01HL090648 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI URBAN, ZSOLT · 2010 to 2018
$4.0M
NHLBI NIH HHS R01 HL090648
6 · The paper itself

Abstract

Inherited cutis laxa, or inelastic, sagging skin is a genetic condition of premature and generalised connective tissue ageing, affecting various elastic components of the extracellular matrix. Several cutis laxa syndromes are inborn errors of metabolism and lead to severe neurological symptoms. In a patient with cutis laxa, a choreoathetoid movement disorder, dysmorphic features and intellectual disability we performed exome sequencing to elucidate the underlying genetic defect. We identified the amino acid substitution R275W in phosphatidylinositol 4-kinase type IIα, caused by a homozygous missense mutation in the PI4K2A gene. We used lipidomics, complexome profiling and functional studies to measure phosphatidylinositol 4-phosphate synthesis in the patient and evaluated PI4K2A deficient mice to define a novel metabolic disorder. The R275W residue, located on the surface of the protein, is involved in forming electrostatic interactions with the membrane. The catalytic activity of PI4K2A in patient fibroblasts was severely reduced and lipid mass spectrometry showed that particular acyl-chain pools of PI4P and PI(4,5)P

Indexed as

Mutation, MissenseAmino Acid SequenceAnimalsChildCutis LaxaFemaleGlycosylationHomozygoteHumansMiceMice, KnockoutMinor Histocompatibility AntigensPedigreePhosphatidylinositolsPhosphotransferases (Alcohol Group Acceptor)SkinMinor Histocompatibility Antigensphosphatidylinositol phosphate 4-kinasePhosphatidylinositolsPhosphotransferases (Alcohol Group Acceptor)choreoathetosiscutis laxainborn error of metabolismmovement disorderneurocutaneous disorderneurometabolismphosphatidyl inositolPI4K2A

Identifiers

PMID32418222
PMCPMC7687218
OpenAlexW3025942802

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.