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The most common genetic cause of ALS is the hexanucleotide repeat expansion in the\n                      <jats:italic>C9orf72<\/jats:italic>\n                      gene, which is associated with earlier disease onset, faster progression, and an increased frequency of cognitive and psychiatric involvement. Data on population-specific characteristics of\n                      <jats:italic>C9orf72<\/jats:italic>\n                      -associated ALS remains limited in Central and Eastern Europe.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Between 2011 and 2024, a total of 959 ALS patients fulfilling established diagnostic criteria were screened for\n                      <jats:italic>C9orf72<\/jats:italic>\n                      repeat expansions at two Hungarian centers. Hexanucleotide repeat expansions were analyzed using repeat-primed long-read PCR. Repeat numbers exceeding 30 were considered pathogenic. Clinical, demographic, and disease course data were retrospectively collected and analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pathogenic\n                      <jats:italic>C9orf72<\/jats:italic>\n                      repeat expansions were identified in 63 of 959 patients, corresponding to a prevalence of 6.57% among Hungarian ALS patients. Bulbar onset was the most common presentation and was associated with faster progression and shorter survival (mean survival: 27.8\u00a0months). Cognitive impairment and psychiatric comorbidities were present in a substantial proportion of patients and were associated with slower functional decline. Regional differences in survival were observed, likely reflecting disparities in healthcare access rather than biological factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study provides the first comprehensive national characterization of\n                      <jats:italic>C9orf72<\/jats:italic>\n                      repeat expansion\u2013associated ALS in Hungary, based on a genetically defined cohort assembled over 13\u00a0years. Despite limitations related to retrospective data collection and cohort size, this ethnically homogeneous dataset offers valuable insight into population-specific clinical and epidemiological features and complements larger international studies. Systematic characterization and longitudinal follow-up of genetically defined, trial-ready ALS cohorts will be essential as targeted therapies for\n                      <jats:italic>C9orf72<\/jats:italic>\n                      -associated ALS approach clinical implementation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s10020-026-01465-w","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T03:56:17Z","timestamp":1776225377000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic epidemiology of C9orf72 repeat expansion associated amyotrophic lateral sclerosis in Hungary"],"prefix":"10.1186","volume":"32","author":[{"given":"Zs\u00f3fia Fl\u00f3ra","family":"Nagy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienn","family":"G\u00e9resi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Grosz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Trombit\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margit","family":"P\u00e1l","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Nagy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e1s","family":"Salamon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Balicza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edvia","family":"D\u00e9zsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Kliv\u00e9nyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rta","family":"Sz\u00e9ll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1ria Judit","family":"Moln\u00e1r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"1465_CR1","doi-asserted-by":"publisher","first-page":"267.e1","DOI":"10.1016\/j.neurobiolaging.2013.07.016","volume":"35","author":"A Alavi","year":"2014","unstructured":"Alavi A, Nafissi S, Rohani M, Shahidi G, Zamani B, Shamshiri H, et al. 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