Background: 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. Case presentation: 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. Discussion: 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.
Missense mutation in ATXN2 gene (c.2860C > T) in an amyotrophic lateral sclerosis patient with aggressive disease phenotype / Ghezzi, A.; Martinelli, I.; Carra, S.; Mediani, L.; Zucchi, E.; Simonini, C.; Gianferrari, G.; Fini, N.; Cereda, C.; Gellera, C.; Pensato, V.; Mandrioli, J.. - In: NEUROLOGICAL SCIENCES. - ISSN 1590-1874. - 43:10(2022), pp. 6087-6090. [10.1007/s10072-022-06229-y]