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Witzel, S.* ; Wagner, M. ; Zhao, C. ; Kandler, K.* ; Graf, E. ; Berutti, R.* ; Oexle, K. ; Brenner, D.* ; Winkelmann, J. ; Ludolph, A.C.*

Fast versus slow disease progression in amyotrophic lateral sclerosis–clinical and genetic factors at the edges of the survival spectrum.

Neurobiol. Aging 119, 117-126 (2022)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Patients with amyotrophic lateral sclerosis (ALS) show substantial differences in disease progression and survival. However, the genetic contribution to the extremes of this spectrum remains poorly characterized. We unbiasedly selected and genotyped 102 ALS patients with very short (<15 months) and 90 with very long survival (>100 months) from the ALS registry of Ulm University using whole-exome sequencing and C9orf72 repeat expansion testing followed by a clinicogenetic correlation analysis. Clinically, groups significantly differed regarding site of disease onset, age at onset, BMI at diagnosis, disease progression rates, and diagnostic latency. We found a monogenic disease cause in 31 patients (16%) without significant differences in patients with short and long survival (19% vs. 13%; p = 0.41), but differences in the genotypic architecture. C9orf72 expansions and FUS mutations were only found in fast progressors, whereas SOD1 variants were frequent in both groups contributing 52% of all monogenic cases–33% among fast and 75% among slow variants. Our genotype-phenotype correlation may be relevant for genetic counseling, estimation of prognosis, and therapeutic decisions.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Amyotrophic Lateral Sclerosis ; Disease Progression ; Exome Sequencing ; Prognostic Factors ; Sod1 ; Survival
ISSN (print) / ISBN 0197-4580
e-ISSN 1558-1497
Zeitschrift Neurobiology of Aging
Quellenangaben Band: 119, Heft: , Seiten: 117-126 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort New York, NY [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
Förderungen Universität Ulm
Deutsche Gesellschaft für Neurologie
Fondation Charcot
Deutsche Forschungsgemeinschaft
Boehringer Ingelheim
Teva Pharmaceutical Industries
Biogen