PXD023584

PXD023584 is an original dataset announced via ProteomeXchange.

Title	Exome reanalysis and proteomic profiling identified TRIP4 as a novel cause of cerebellar hypoplasia and spinal muscular atrophy (PCH1)
Description	TRIP4 is one of the subunits of the transcriptional coregulator ASC-1, a ribonucleoprotein complex that participates in transcriptional coactivation and RNA processing events. Recessive variants in the TRIP4 gene have been associated with spinal muscular atrophy with bone fractures as well as a severe form of congenital muscular dystrophy. Here we present the diagnostic journey of a patient with cerebellar hypoplasia and spinal muscular atrophy (PCH1) and congenital bone fractures. Initial exome sequencing analysis revealed no candidate variants. Reanalysis of the exome data by inclusion in the Solve-RD project resulted in the identification of a homozygous stop-gain variant in the TRIP4 gene, previously reported as disease-causing. This highlights the importance of analysis reiteration and improved and updated bioinformatic pipelines. Proteomic profile of the patient’s fibroblasts showed altered RNA-processing and impaired exosome activity supporting the pathogenicity of the detected variant. In addition, we identified a novel genetic form of PCH1, further strengthening the link of this characteristic phenotype with altered RNA metabolism.
HostingRepository	PRIDE
AnnounceDate	2022-02-16
AnnouncementXML	Submission_2022-02-16_13:20:20.494.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas Hentschel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-14 01:49:20	ID requested
⏵ 1	2022-02-16 13:20:21	announced

T, ö, pf A, Pyle A, Griffin H, Matalonga L, Schon K, Sickmann A, Schara-Schmidt U, Hentschel A, Chinnery PF, K, ö, lbel H, Roos A, Horvath R, Cohen E, Cuesta I, Danis D, Denomm, é, -Pichon AS, Duffourd Y, Gilissen C, Johari M, Laurie S, Li S, Nelson I, Paramonov I, Peters S, Prasanth S, Robinson P, Sablauskas K, Savarese M, Steyaert W, van der Velde JK, Vitobello A, Baets J, Beijer D, Bonne G, Cossins J, Evangelista T, Ferlini A, Hackman P, Hanna MG, Houlden H, Lau J, Lochm, ü, ller H, Macken WL, Musacchia F, Nascimento A, Natera-de Benito D, Nigro V, Piluso G, Pini V, Pitceathly RDS, Polavarapu K, Cruz PMR, Sarkozy A, Selvatici R, Thompson R, Torella A, Udd B, Van de Vondel L, Vandrovcova J, Zaharieva I, Exome reanalysis and proteomic profiling identified TRIP4 as a novel cause of cerebellar hypoplasia and spinal muscular atrophy (PCH1). Eur J Hum Genet, 29(9):1348-1353(2021) [pubmed]

submitter keyword: SOLVE-RD, exome reanalysis, proteogenomics, TRIP4, PCH1

Andreas Hentschel
contact affiliation	Department of Bioanalytics, Leibniz-Institut für Analytische Wissenschaften ISAS e.V., Dortmund, Germany.
contact email	andreas.hentschel@isas.de
lab head
Andreas Hentschel
contact affiliation	Leibniz Institut für Analytische Wissenschaften
contact email	andreas.hentschel@isas.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023584
     1. Label: PRIDE project
     2. Name: Exome reanalysis and proteomic profiling identified TRIP4 as a novel cause of cerebellar hypoplasia and spinal muscular atrophy (PCH1)