PXD067750

PXD067750 is an original dataset announced via ProteomeXchange.

Title	PURA Syndrome as a Congenital Myasthenic Disorder: Evidence from Muscle Morphology, Proteomics, and Blood Biomarkers
Description	Dominant PURA variants cause a neurodevelopmental disorder with hypotonia, cognitive impairment, and variable neuromuscular symptoms. Clinical response to pyridostigmine suggests neuromuscular junction (NMJ) involvement, but NMJ architecture, molecular mechanisms, and minimally invasive biomarkers remain unclear. This study investigated NMJ pathology in PURA patients using integrated clinical, histological, ultrastructural, and molecular approaches. Patients presented with hypotonia, ptosis, ocular weakness, and myopathic facies, consistent with impaired neuromuscular transmission. Electron microscopy revealed vesicle accumulation and NMJ alterations, providing the first ultrastructural evidence of NMJ pathology in PURA. Muscle proteomics showed reduced PURA protein and dysregulation of transcriptional regulation, vesicle transport, extracellular matrix remodeling, and complement activation. qPCR confirmed POSTN and PHGDH upregulation among others. Serum analyses demonstrated elevated TSP4, identifying the first blood biomarker for PURA-associated NMJ dysfunction. EV proteomics revealed dysregulated immunoglobulins, complement components, and novel candidates including NOTCH2, TARSH, and PON1.
HostingRepository	PRIDE
AnnounceDate	2026-02-02
AnnouncementXML	Submission_2026-02-01_21:54:40.299.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: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF; timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-26 09:59:38	ID requested
⏵ 1	2026-02-01 21:54:41	announced

10.1007/s00415-026-13621-7;

Mroczek M, Preusse C, Hentschel A, Chro, ś, ci, ń, ska-Krawczyk M, Bielak M, Sobolewska A, Della Marina A, Hila A, Iyadurai S, Kraft F, Chetty VK, Muhmann D, Ruck T, Goebel HH, Schara-Schmidt U, Dobelmann V, Thakur BK, Stenzel W, Roos A, Exploring molecular signatures in PURA syndrome using muscle proteomics and serum biomarkers. J Neurol, 273(2):94(2026) [pubmed]

submitter keyword: muscle proteomics, Thrombospondin-4 (TSP4), Target of Nesh-SH3 (TARSH),Congenital myasthenic syndrome (CMS), extracellular vesicles in neuromuscular diseases, Periostin (POSTN)

Albert Sickmann
contact affiliation	Proteomics, Leibniz-Institut für analytische Wissenschaften -ISAS - e.V., Germany
contact email	albert.sickmann@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. PXD067750
     1. Label: PRIDE project
     2. Name: PURA Syndrome as a Congenital Myasthenic Disorder: Evidence from Muscle Morphology, Proteomics, and Blood Biomarkers