Scholarlink

Background <p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss. The most common genetic cause of ALS is the hexanucleotide repeat expansion in the <i>C9orf72</i> 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 <i>C9orf72</i>-associated ALS remains limited in Central and Eastern Europe.</p> Methods <p>Between 2011 and 2024, a total of 959 ALS patients fulfilling established diagnostic criteria were screened for <i>C9orf72</i> 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.</p> Results <p>Pathogenic <i>C9orf72</i> 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&#xa0;months). 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.</p> Conclusions <p>This study provides the first comprehensive national characterization of <i>C9orf72</i> repeat expansion–associated ALS in Hungary, based on a genetically defined cohort assembled over 13&#xa0;years. 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 <i>C9orf72</i>-associated ALS approach clinical implementation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Genetic epidemiology of C9orf72 repeat expansion associated amyotrophic lateral sclerosis in Hungary

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月15日

查看全文
  • Zsófia Flóra Nagy,
  • Adrienn Géresi,
  • Zoltán Grosz,
  • Barbara Trombitás,
  • Margit Pál,
  • Dominika Nagy,
  • András Salamon,
  • Péter Balicza,
  • Lívia Dézsi,
  • Péter Klivényi,
  • Márta Széll,
  • Mária Judit Molnár

摘要

Background

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss. The most common genetic cause of ALS is the hexanucleotide repeat expansion in the C9orf72 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 C9orf72-associated ALS remains limited in Central and Eastern Europe.

Methods

Between 2011 and 2024, a total of 959 ALS patients fulfilling established diagnostic criteria were screened for C9orf72 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.

Results

Pathogenic C9orf72 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 months). 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.

Conclusions

This study provides the first comprehensive national characterization of C9orf72 repeat expansion–associated ALS in Hungary, based on a genetically defined cohort assembled over 13 years. 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 C9orf72-associated ALS approach clinical implementation.