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A novel splice site FUS mutation in a familial ALS case: effects on protein expression

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN: 2167-9223, Vol: 23, Issue: 1-2, Page: 128-136
2022
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A novel splice site FUS mutation in a familial ALS case: effects on protein expression.

Amyotroph Lateral Scler Frontotemporal Degener. 2021 Apr 21;:1-9. Authors: Canosa A, Lomartire A, De Marco G, Grassano M, Brunetti M, Manera U, Vasta R, Salamone P, Fuda G, Sbaiz L, Gallone S, Moglia C, Calvo A, Chiò A PubMed: 33879000 Submit Comment

Article Description

Objective: To investigate the impact of a novel heterozygous FUS mutation in the acceptor splice site of intron 14 (c.1542 − 1 g > t) on protein expression in Peripheral Blood Mononuclear Cells (PBMC) from a familial ALS patient. Methods: PBMC were isolated for mRNA analysis (cDNA synthesis, sequencing and one-step RT-PCR), Western Immunoblot (WI), and Immunofluorescence (IF). Results: cDNA analysis revealed the skipping of exon 15 and a premature stop codon at c.228. RT-PCR showed reduced FUS mRNA by more than half compared to a healthy control (HC) and an ALS patient without genetic mutations (wtALS). In WI FUS band intensity in the proband was 30–50% compared to HC and wtALS. An antibody expected to detect only the wild-type protein did not reveal any reduction of FUS band intensity compared to the other antibodies. IF showed no difference among HC, wtALS, and the proband. Discussion: The reduction of FUS mRNA and protein in PBMC suggests the absence of the truncated protein, probably due to nonsense-mediated decay, leading to loss of function.

Bibliographic Details

Canosa, Antonio; Lomartire, Annarosa; De Marco, Giovanni; Grassano, Maurizio; Brunetti, Maura; Manera, Umberto; Vasta, Rosario; Salamone, Paolina; Fuda, Giuseppe; Sbaiz, Luca; Gallone, Salvatore; Moglia, Cristina; Calvo, Andrea; Chiò, Adriano

Informa UK Limited

Neuroscience; Medicine

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