PXD053070

PXD053070 is an original dataset announced via ProteomeXchange.

Title	Giant Axonal Neuropathy (GAN): Cross-sectional data on phenotypes, genotypes and proteomics signature from a German-Austrian-Swiss cohort
Description	Giant Axon Neuropathy (GAN) is a progressive neurodegenerative disease characterised by involvement of peripheral and central nervous system frequently associated with frizzy hair. The phenotype is caused by bi-allelic variants in the GAN gene, leading to loss of functional gigaxonin proteins.. Thus, far the disease cannot be cured, but a first clinical gene therapy trial in the US was currently completed. So far, there has been no systematic reporting of GAN patients in German-speaking countries. Therefore, we conducted a survey using an e-mail list of German-speaking child neurologists of the so-called DACH region reflecting Germany, Austria and Switzerland. Based on their feedback, clinical, genetic and epidemiological data were collected using a standardised data collection form in turn enabling the collection of comprehensive and detailed epidemiological, clinical and genetic information from a total of 15 patients representing one of the largest cohorts systematically described thus far. Average age of patients was 11.7 years at the time of data collection. In line with the frequency of homozygous variants, the majority were of Syrian origin and of consanguineous relationships. In 14 patients, diagnosis was confirmed by molecular genetics, revealing eight different GAN variants, four being reported as pathogenic in literature. 13 patients had a classical GAN phenotype, one was classified as mild whereas another one was too young to draw final clinical conclusions. Proteomics of white blood cells derived from four patients revealed was conducted to obtain unbiased insights into the underlying pathophysiology and revealed dysregulation of 111 proteins implicated in diverse biological processes. Of note diverse of these proteins are known to be crucial for proper synaptic function and transmission and affection of intermediate filament organization and proteolysis is in line with the known functions of gigaxonin. In view of a potential genetic treatment option, these data on the natural course of the disease are important for study design in preparation for gene therapy trials in Europe and moreover provide a catalogue of proteins serving as minimal invasive but cellular biomarkers.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-06_19:16:00.466.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	2024-06-13 02:59:09	ID requested
⏵ 1	2025-05-06 19:16:01	announced

10.1007/s00415-024-12744-z;

Gangfu, ß A, Goj G, Polz S, Della Marina A, Hentschel A, Ahlbory K, Deba T, Kotzaeridou U, Schuler E, Pechmann A, Diebold U, Kurlemann G, Heinzkyll L, Schmitt D, Rostasy K, Ruck T, B, ö, hm J, Roos A, Schara-Schmidt U, Giant axonal neuropathy (GAN): cross-sectional data on phenotypes, genotypes, and proteomic signature from a German cohort. J Neurol, 272(1):63(2024) [pubmed]

submitter keyword: White blood cells,GAN, Proteomics

Andreas Hentschel
contact affiliation	Proteomics, Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V., 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

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/2025/05/PXD053070

PRIDE project URI

• PRIDE
  1. PXD053070
     1. Label: PRIDE project
     2. Name: Giant Axonal Neuropathy (GAN): Cross-sectional data on phenotypes, genotypes and proteomics signature from a German-Austrian-Swiss cohort