Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Mar 4;16(3):309.
doi: 10.3390/genes16030309.

Phenotypical Characterization of C9ALS Patients from the Emilia Romagna Registry of ALS: A Retrospective Case-Control Study

Andrea Ghezzi  1   2 , Giulia Gianferrari  1   2 , Elisa Baldassarri  1 , Elisabetta Zucchi  1   2 , Ilaria Martinelli  2 , Veria Vacchiano  3 , Luigi Bonan  4 , Lucia Zinno  5 , Andi Nuredini  5 , Elena Canali  6 , Matteo Gizzi  7 , Emilio Terlizzi  8 , Doriana Medici  9 , Elisabetta Sette  10 , Marco Currò Dossi  11 , Simonetta Morresi  12 , Mario Santangelo  13 , Alberto Patuelli  14 , Marco Longoni  14 , Patrizia De Massis  15 , Salvatore Ferro  16 , Nicola Fini  2 , Cecilia Simonini  2 , Serena Carra  1 , Giovanna Zamboni  1   2 , Jessica Mandrioli  1   2
Affiliations

Phenotypical Characterization of C9ALS Patients from the Emilia Romagna Registry of ALS: A Retrospective Case-Control Study

Andrea Ghezzi et al. Genes (Basel). .

Abstract

Background/objectives: C9ORF72 expansion is associated with significant phenotypic heterogeneity. This study aimed to characterize the clinical features of C9ALS patients from the Emilia Romagna ALS registry (ERRALS) and compare them with non-mutated ALS (nmALS) patients matched for sex, age at onset, and diagnostic delay, sourced from the same register.

Methods: In total, 67 C9ALS patients were compared to 201 nmALS. Clinical data, phenotype, and prognostic factors were analyzed in the two groups and within the C9ALS group after stratification by sex.

Results: C9ALS patients displayed a higher disease progression rate and shorter times to gastrostomy and invasive ventilation, despite no differences in overall survival. Female C9ALS had a more severe bulbar and upper motor neuron involvement compared to males. Cognitive and behavioral symptoms were more common in the C9ALS group, and the former was an independent prognostic factor. Prevalences of, autoimmune diseases, and dyslipidemia were significantly higher among C9ALS patients.

Conclusions: In our dataset, we show an overall increased disease progression rate in C9ALS patients and hint at sex-specific discrepancies in some phenotypical characteristics. We also suggest a possible clinically relevant involvement of C9ORF72 expansion in metabolism and autoimmunity.

Keywords: C9ORF72; amyotrophic lateral sclerosis; clinical features; phenotype; population-based study.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart showing patient selection.
Figure 2
Figure 2
Kaplan–Meier showing survival in C9ALS and nmALS patients.
Figure 3
Figure 3
Kaplan–Meier showing survival in male and female C9ALS patients.
See this image and copyright information in PMC

References

    1. Masrori P., Van Damme P. Amyotrophic lateral sclerosis: A clinical review. Eur. J. Neurol. 2020;27:1918–1929. doi: 10.1111/ene.14393. - DOI - PMC - PubMed
    1. Greaves C.V., Rohrer J.D. An update on genetic frontotemporal dementia. J. Neurol. 2019;266:2075–2086. doi: 10.1007/s00415-019-09363-4. - DOI - PMC - PubMed
    1. Balendra R., Isaacs A.M. C9orf72-mediated ALS and FTD: Multiple pathways to disease. Nat. Rev. Neurol. 2018;14:544–558. doi: 10.1038/s41582-018-0047-2. - DOI - PMC - PubMed
    1. Murphy N.A., Arthur K.C., Tienari P.J., Houlden H., Chiò A., Traynor B.J. Age-related penetrance of the C9orf72 repeat expansion. Sci. Rep. 2017;7:2116. doi: 10.1038/s41598-017-02364-1. - DOI - PMC - PubMed
    1. Zampatti S., Peconi C., Campopiano R., Gambardella S., Caltagirone C., Giardina E. C9orf72-Related Neurodegenerative Diseases: From Clinical Diagnosis to Therapeutic Strategies. Front. Aging Neurosci. 2022;14:907122. doi: 10.3389/fnagi.2022.907122. - DOI - PMC - PubMed

LinkOut - more resources