{"doi":"10.1007/s00415-024-12744-z","title":"Giant axonal neuropathy (GAN): cross-sectional data on phenotypes, genotypes, and proteomic signature from a German cohort","abstract":"<jats:title>Abstract</jats:title>\n          <jats:p>Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease affecting the peripheral and central nervous system and is caused by bi-allelic variants in the <jats:italic>GAN</jats:italic> gene, leading to loss of functional gigaxonin protein. A treatment does not exist, but a first clinical trial using a gene therapy approach has recently been completed. Here, we conducted the first systematic study of GAN patients treated by German-speaking child neurologists. We collected clinical, genetic, and epidemiological data from a total of 15 patients representing one of the largest cohorts described thus far. Average age of patients was 11.7 years at inclusion. The most frequently reported symptoms (HPO coded) were gait disturbance and muscle weakness, abnormality of muscle size, and abnormal reflexes. In line with the frequency of homozygous variants, in five families, parents reported being at least distantly related. In 14 patients, diagnosis was confirmed by molecular genetic testing, revealing eight different <jats:italic>GAN</jats:italic> variants, four being reported as pathogenic in the literature. Proteomics of white blood cells derived from four patients 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 is known to be crucial for proper synaptic function and transmission and affection of intermediate filament organisation and proteolysis, which is in line with the known functions of gigaxonin.</jats:p>","journal":"Journal of Neurology","year":2025,"id":617762,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":4,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1593264,"name":"Guido Goj","orcid":null,"position":1,"is_corresponding":false},{"id":1593271,"name":"Silke Polz","orcid":null,"position":2,"is_corresponding":false},{"id":236845,"name":"Adela Della Marina","orcid":"0000-0003-0737-6142","position":3,"is_corresponding":false},{"id":1218634,"name":"Andreas Hentschel","orcid":"0000-0002-0272-9220","position":4,"is_corresponding":false},{"id":1593274,"name":"Katja Ahlbory","orcid":null,"position":5,"is_corresponding":false},{"id":1593275,"name":"Timo Deba","orcid":null,"position":6,"is_corresponding":false},{"id":331213,"name":"Urania Kotzaeridou","orcid":"0000-0002-6537-2820","position":7,"is_corresponding":false},{"id":1010267,"name":"Elisabeth Schuler","orcid":null,"position":8,"is_corresponding":false},{"id":1029174,"name":"Astrid Pechmann","orcid":null,"position":9,"is_corresponding":false},{"id":1593278,"name":"Uta Diebold","orcid":null,"position":10,"is_corresponding":false},{"id":657691,"name":"Gerhard Kurlemann","orcid":null,"position":11,"is_corresponding":false},{"id":1593279,"name":"Lucas Heinzkyll","orcid":null,"position":12,"is_corresponding":false},{"id":1593280,"name":"Dirk Schmitt","orcid":null,"position":13,"is_corresponding":false},{"id":1593281,"name":"Kevin Rostasy","orcid":null,"position":14,"is_corresponding":false},{"id":707714,"name":"Tobias Ruck","orcid":"0000-0001-6332-8650","position":15,"is_corresponding":false},{"id":457096,"name":"Johann Böhm","orcid":"0000-0001-8019-9504","position":16,"is_corresponding":false},{"id":383310,"name":"Andreas Roos","orcid":"0000-0003-2833-0928","position":17,"is_corresponding":false},{"id":1593282,"name":"Ulrike Schara-Schmidt","orcid":null,"position":18,"is_corresponding":false},{"id":627914,"name":"Andrea Gangfuß","orcid":"0000-0002-9975-0092","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Giant axonal neuropathy (GAN): cross-sectional data on phenotypes, genotypes, and proteomic signature from a German cohort","abstract":"<jats:title>Abstract</jats:title>\n          <jats:p>Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease affecting the peripheral and central nervous system and is caused by bi-allelic variants in the <jats:italic>GAN</jats:italic> gene, leading to loss of functional gigaxonin protein. A treatment does not exist, but a first clinical trial using a gene therapy approach has recently been completed. Here, we conducted the first systematic study of GAN patients treated by German-speaking child neurologists. We collected clinical, genetic, and epidemiological data from a total of 15 patients representing one of the largest cohorts described thus far. Average age of patients was 11.7 years at inclusion. The most frequently reported symptoms (HPO coded) were gait disturbance and muscle weakness, abnormality of muscle size, and abnormal reflexes. In line with the frequency of homozygous variants, in five families, parents reported being at least distantly related. In 14 patients, diagnosis was confirmed by molecular genetic testing, revealing eight different <jats:italic>GAN</jats:italic> variants, four being reported as pathogenic in the literature. Proteomics of white blood cells derived from four patients 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 is known to be crucial for proper synaptic function and transmission and affection of intermediate filament organisation and proteolysis, which is in line with the known functions of gigaxonin.</jats:p>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39680150","pmcid":"PMC11649756","openalex_id":"https://openalex.org/W4405424256","authors":[],"funders":[{"funder_name":"EFRE/JTF B2B-RARE","grant_id":"EFRE-20800340","title":null},{"funder_name":"Universitätsklinikum Essen","grant_id":"","title":null}],"total_grants":2,"fwci":0.7559,"citation_percentile":0.69039687,"influential_citations":0,"citation_trend":[{"year":2025,"count":2},{"year":2026,"count":2}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s00415-024-12744-z.pdf","host_type":"journal"},{"url":"https://link.springer.com/content/pdf/10.1007/s00415-024-12744-z.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s00415-024-12744-z/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s00415-024-12744-z","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39680150","host_type":"repository"},{"url":"https://hal.science/hal-05027177","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11649756","host_type":"repository"},{"url":"https://link.springer.com/10.1007/s00415-024-12744-z","host_type":"repository"},{"url":"https://hal.science/hal-05027177/document","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11649756/pdf/415_2024_Article_12744.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11649756","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11649756?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Hereditary Neurological Disorders","Skin and Cellular Biology Research","Neurological diseases and metabolism","Humans","Giant Axonal Neuropathy","Child","Male","Germany","Female","Phenotype","Adolescent","Cohort Studies","Proteomics","Cross-Sectional Studies","Genotype","Child, Preschool","Cytoskeletal Proteins"],"mesh_terms":["Adolescent","Child","Child, Preschool","Cross-Sectional Studies","Cytoskeletal Proteins","Female","Genotype","Germany","Humans","Male","Phenotype","Cohort Studies","Proteomics","Giant Axonal Neuropathy"],"keywords":["Neurology","Cohort","Biology","Phenotype","Disease","Peripheral neuropathy","Genotype","Epidemiology","Abnormality","Bioinformatics","Genetics","Neuroscience","Medicine","Gene","Pathology","Endocrinology","Diabetes mellitus","Psychiatry","Consanguinity","Proteomics","Giant Axonal Neuropathy","Gigaxonin","Gan Gene","Neurodegenrative"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"omim"},{"name":"pxd"},{"name":"uniprot"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T02:33:12.590439Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}