| Title: |
Clinical and genetic features of amyotrophic lateral sclerosis patients with C9orf72mutations |
| Authors: |
Wiesenfarth, Maximilian; Günther, Kornelia; Müller, Kathrin; Witzel, Simon; Weiland, Ulrike; Mayer, Kristina; Herrmann, Christine; Brenner, David; Schuster, Joachim; Freischmidt, Axel; Lulé, Dorothée; Meyer, Thomas; Regensburger, Martin; Grehl, Torsten; Emmer, Alexander; Petri, Susanne; Großkreutz, Julian; Rödiger, Annekathrin; Steinbach, Robert; Klopstock, Thomas; Reilich, Peter; Schöberl, Florian; Wolf, Joachim; Hagenacker, Tim; Weyen, Ute; Zeller, Daniel; Ludolph, Albert C; Dorst, Johannes |
| Source: |
Brain Communications ; volume 5, issue 2 ; ISSN 2632-1297 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2023 |
| Description: |
An expansion of the GGGGCC hexanucleotide in the non-coding region of C9orf72 represents the most common cause of familial amyotrophic lateral sclerosis. The objective was to describe and analyse the clinical and genetic features of amyotrophic lateral sclerosis patients with C9orf72 mutations in a large population. Between November 2011 and December 2020, clinical and genetic characteristics of n = 248 patients with amyotrophic lateral sclerosis carrying C9orf72 mutations were collected from the clinical and scientific network of German motoneuron disease centres. Clinical parameters included age of onset, diagnostic delay, family history, neuropsychological examination, progression rate, phosphorylated neurofilament heavy chain levels in CSF and survival. The number of repeats was correlated with the clinical phenotype. The clinical phenotype was compared to n = 84 patients with SOD1 mutations and n = 2178 sporadic patients without any known disease-related mutations. Patients with C9orf72 featured an almost balanced sex ratio with 48.4% (n = 120) women and 51.6% (n = 128) men. The rate of 33.9% patients (n = 63) with bulbar onset was significantly higher compared to sporadic (23.4%, P = 0.002) and SOD1 patients (3.1%, P < 0.001). Of note, 56.3% (n = 138) of C9orf72, but only 16.1% of SOD1 patients reported a negative family history (P < 0.001). The GGGGCC hexanucleotide repeat length did not influence the clinical phenotypes. Age of onset (58.0, interquartile range 52.0–63.8) was later compared to SOD1 (50.0, interquartile range 41.0–58.0; P < 0.001), but earlier compared to sporadic patients (61.0, interquartile range 52.0–69.0; P = 0.01). Median survival was shorter (38.0 months) compared to SOD1 (198.0 months, hazard ratio 1.97, 95% confidence interval 1.34–2.88; P < 0.001) and sporadic patients (76.0 months, hazard ratio 2.34, 95% confidence interval 1.64–3.34; P < 0.001). Phosphorylated neurofilament heavy chain levels in CSF (2880, interquartile range ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/braincomms/fcad087 |
| DOI: |
10.1093/braincomms/fcad087/49572743/fcad087.pdf |
| Availability: |
https://doi.org/10.1093/braincomms/fcad087; https://academic.oup.com/braincomms/advance-article-pdf/doi/10.1093/braincomms/fcad087/49572743/fcad087.pdf; https://academic.oup.com/braincomms/article-pdf/5/2/fcad087/49717037/fcad087.pdf |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.1399E761 |
| Database: |
BASE |