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

Autor: Simon Witzel, Matias Wagner, Chen Zhao, Katharina Kandler, Elisabeth Graf, Riccardo Berutti, Konrad Oexle, David Brenner, Juliane Winkelmann, Albert C. Ludolph
Rok vydání: 2022
Předmět:
Zdroj: Neurobiology of aging 119, 117-126 (2022). doi:10.1016/j.neurobiolaging.2022.07.005
ISSN: 0197-4580
DOI: 10.1016/j.neurobiolaging.2022.07.005
Popis: 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 (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.
Databáze: OpenAIRE
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