Dataset Information

PURA Syndrome as a Congenital Myasthenic Disorder: Evidence from Muscle Morphology, Proteomics, and Blood Biomarkers

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum, Muscle

SUBMITTER: Andreas Hentschel

LAB HEAD: Albert Sickmann

PROVIDER: PXD067750 | Pride | 2026-02-02

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20230705_112850_NME_Muscle_PURA_N238-20_vs_IOPD_Ctrl.sne	Other
	20230705_113222_NME_Muscle_PURA_N238-20_vs_IOPD_Ctrl_Report.csv	Csv
	Analysis_VesikelVenki_PURA_combined_fractions.csv	Csv
	EV_measurment_files_TimsTof.zip	Other
	QExactiveHF02_15701_N238-20_PURA.raw	Raw

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Publications

Exploring molecular signatures in PURA syndrome using muscle proteomics and serum biomarkers.

Mroczek Magdalena M Preusse Corinna C Hentschel Andreas A Chrościńska-Krawczyk Magdalena M Bielak Michał M Sobolewska Adela A Della Marina Adela A Hila Anisa A Iyadurai Stanley S Kraft Florian F Chetty Venkatesh Kumar VK Muhmann David D Ruck Tobias T Goebel Hans-Hilmar HH Schara-Schmidt Ulrike U Dobelmann Vera V Thakur Basant Kumar BK Stenzel Werner W Roos Andreas A

Journal of neurology 20260123 2

<h4>Background and purpose</h4>Dominant PURA variants (encoding purine-rich element-binding protein A) cause a neurodevelopmental disorder with hypotonia, cognitive impairment, and variable neuromuscular symptoms. Clinical presentations and response to pyridostigmine, moreover, highlighted neuromuscular junction (NMJ) involvement. However, NMJ architecture, underlying molecular mechanisms, and potential minimally invasive biomarkers in PURA syndrome remain poorly characterized. This study aimed ...[more]

PMID: 41575592

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