Missense mutation in ATXN2 gene (c.2860C > T) in an amyotrophic lateral sclerosis patient with aggressive disease phenotype.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2022 Oct

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ALS symptoms have been previously described only in the context of ATXN2 CAG expansions, whereas missense mutations of the gene have never been described in ALS patients. We identified a novel missense mutation (c.2860C > T) of ATXN2, for which in silico analysis showed a possible pathogenic effect on protein expression, in a patient presenting an aggressive disease phenotype. Our findings raise the possibility for unknown genetic factors interacting with ATXN2 mutations, or for an autonomous pathogenic role for this specific point mutation in ATXN2 gene in driving the clinical phenotype toward ALS. We also found that stress granules in the fibroblasts from the patient entrapped higher amounts of defective ribosomal products compared to fibroblasts from three healthy subjects, suggesting that ATXN2 mutation-related toxicity may have implication in protein quality control. © 2022. Fondazione Società Italiana di Neurologia.

Citation

Andrea Ghezzi, Ilaria Martinelli, Serena Carra, Laura Mediani, Elisabetta Zucchi, Cecilia Simonini, Giulia Gianferrari, Nicola Fini, Cristina Cereda, Cinzia Gellera, Viviana Pensato, Jessica Mandrioli. Missense mutation in ATXN2 gene (c.2860C > T) in an amyotrophic lateral sclerosis patient with aggressive disease phenotype. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2022 Oct;43(10):6087-6090