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Document type:
Article; Journal Article; Research Support, Non-U.S. Gov't
Author(s):
Witzel, Simon; Wagner, Matias; Zhao, Chen; Kandler, Katharina; Graf, Elisabeth; Berutti, Riccardo; Oexle, Konrad; Brenner, David; Winkelmann, Juliane; Ludolph, Albert C
Title:
Fast versus slow disease progression in amyotrophic lateral sclerosis-clinical and genetic factors at the edges of the survival spectrum.
Abstract:
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.
Journal title abbreviation:
Neurobiol Aging
Year:
2022
Journal volume:
119
Pages contribution:
117-126
Fulltext / DOI:
doi:10.1016/j.neurobiolaging.2022.07.005
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/35933239
Print-ISSN:
0197-4580
TUM Institution:
303; Institut für Humangenetik; Lehrstuhl für Neurogenetik (N.N.)
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