PXD071037-1

PXD071037 is an original dataset announced via ProteomeXchange.

Title	Combined Histological and Proteomic Analysis Reveals Muscle Denervation in KMT5B-Related Neurodevelopmental Disorder: A Case Report
Description	Background: Patients with neurodevelopmental and neuromuscular disorders often show overlapping clinical phenotypes. Pathogenic variants in KMT5B, a histone lysine methyltransferase, have been linked to neurodevelopmental disorders, yet their effects on human skeletal muscle remain unexplored. We report a patient with KMT5B-linked disease who presented to a neuromuscular specialty clinic with significant involvement of skeletal muscle, where a multi-omics approach established the genetic diagnosis and revealed neuromuscular findings relevant for diagnosis, care and rehabilitation. Methods: Whole-exome sequencing was performed from blood and data was analyzed using the RD-Connect Genome Phenome Analysis Platform. Histological analysis and proteomic profiling were performed on muscle tissue. Results: Whole-exome sequencing revealed a pathogenic heterozygous variant (c.554_557del, p.Tyr185Cysfs*27) in KMT5B. Histological examination revealed fiber-type grouping, angular fibers, increased fast-twitch fiber proportion, and lipid droplet accumulation, indicative of muscle denervation. Proteomic profiling identified 77 dysregulated proteins, including upregulation of sarcomeric proteins, mitochondrial and glycolytic enzymes, acute-phase and complement factors, and extracellular matrix components, reflecting structural remodeling, metabolic adaptation, and inflammatory activation. These findings align with phenotypes observed in Kmt5b mouse models, supporting a role of KMT5B in neuromuscular function.
HostingRepository	PRIDE
AnnounceDate	2026-01-05
AnnouncementXML	Submission_2026-01-04_16:33:28.029.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; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-21 05:21:57	ID requested
⏵ 1	2026-01-04 16:33:29	announced

10.3390/jcm14248636;

Aksel Kilicarslan O, Gangfu, ß A, K, ö, lbel H, Muhmann D, Polavarapu K, Thompson R, Schmitt LI, Lessard L, Chen L, Eisenk, ö, lbl A, Schara-Schmidt U, Hentschel A, Lochm, ü, ller H, Roos A, Combined Histological and Proteomic Analysis Reveals Muscle Denervation in KMT5B-Related Neurodevelopmental Disorder: A Case Report. J Clin Med, 14(24):(2025) [pubmed]

submitter keyword: KMT5B

muscle denervation in neurodevelopmental disorders

muscle proteomics

fast-twitch fiber predominance

hypotonia

case report

Prof. Dr. 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. PXD071037
     1. Label: PRIDE project
     2. Name: Combined Histological and Proteomic Analysis Reveals Muscle Denervation in KMT5B-Related Neurodevelopmental Disorder: A Case Report