PXD011355

PXD011355 is an original dataset announced via ProteomeXchange.

Title	De novo heterozygous variants in POLR2A cause a neurodevelopmental syndrome with infantile-onset hypotonia
Description	ABSTRACT POLR2A encodes RPB1, the largest subunit of the RNA polymerase II (pol II) complex, which is responsible for transcription of all ~21,000 protein-encoding genes. Here we describe the first fifteen patients harboring de novo heterozygous variants in POLR2A. The majority presents with profound infantile onset hypotonia and developmental delay. Missense variants that were expected to exert only mild structural effects, lead to malfunctioning RPB1, thereby inducing a dominant negative effect on pol II function. Intriguingly, these patients presented with a severe clinical phenotype. Conversely, variants expected to result in loss-of-function, leading to reduced availability of RPB1 were better tolerated: these patients exhibited the mildest phenotypes.
HostingRepository	PRIDE
AnnounceDate	2019-09-02
AnnouncementXML	Submission_2019-09-02_06:36:11.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Harmjan Vos
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-10-15 03:45:46	ID requested
⏵ 1	2019-09-02 06:36:13	announced

Haijes HA, Koster MJE, Rehmann H, Li D, Hakonarson H, Cappuccio G, Hancarova M, Lehalle D, Reardon W, Schaefer GB, Lehman A, van de Laar IMBH, Tesselaar CD, Turner C, Goldenberg A, Patrier S, Thevenon J, Pinelli M, Brunetti-Pierri N, Prchalov, á D, Havlovicov, á M, Vlckova M, Sedl, á, č, ek Z, Lopez E, Ragoussis V, Pagnamenta AT, Kini U, Vos HR, van Es RM, van Schaik RFMA, van Essen TAJ, Kibaek M, Taylor JC, Sullivan J, Shashi V, Petrovski S, Fagerberg C, Martin DM, van Gassen KLI, Pfundt R, Falk MJ, McCormick EM, Timmers HTM, van Hasselt PM, De Novo Heterozygous POLR2A Variants Cause a Neurodevelopmental Syndrome with Profound Infantile-Onset Hypotonia. Am J Hum Genet, 105(2):283-301(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: RNA polymerase II, RPB1, POLR2A, de novo heterozygous variants

P.M. van Hasselt
contact affiliation	Wilhelmina Children’s Hospital University Medical Center Utrecht Lundlaan 6 3584 EA Utrecht The Netherlands
contact email	p.vanhasselt@umcutrecht.nl
lab head
Harmjan Vos
contact affiliation	University Medical Center Utrecht Dept. Molecular Cancer Research
contact email	h.r.vos-3@umcutrecht.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/09/PXD011355

PRIDE project URI

• PRIDE
  1. PXD011355
     1. Label: PRIDE project
     2. Name: De novo heterozygous variants in POLR2A cause a neurodevelopmental syndrome with infantile-onset hypotonia