De novo nonsense mutation of the FUS gene in an apparently familial amyotrophic lateral sclerosis case.
Mutations in C9ORF72, SOD1, TARDBP, and FUS genes account for approximately two-third of familial cases and 5% of sporadic amyotrophic lateral sclerosis (ALS) cases. We present the first case of an ALS patient carrying a de novo nonsense mutation in exon 14 of the FUS gene (c.1483c>t; p.R495X) with an apparently familial ALS. This mutation causes a phenotype characterized by a young age at onset, a rapid course (<24 months), and a bulbar onset with early respiratory involvement with a predominant lower motor neuron disease. De novo mutations could account for a sizable number of apparently sporadic ALS patients carrying mutations of ALS-related genes.
"Rita Levi Montalcini" Department of Neuroscience, ALS Center, University of Torino, Torino, Italy.
Andrea
A
Calvo
"Rita Levi Montalcini" Department of Neuroscience, ALS Center, University of Torino, Torino, Italy.
Cristina
C
Moglia
"Rita Levi Montalcini" Department of Neuroscience, ALS Center, University of Torino, Torino, Italy.
Antonio
A
Canosa
Laboratory of Molecular Genetics, Azienda Ospedaliera Città della Salute e della Scienza, Torino, Italy.
Maura
M
Brunetti
Laboratory of Molecular Genetics, Azienda Ospedaliera Città della Salute e della Scienza, Torino, Italy.
Marco
M
Barberis
Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Bryan J
BJ
Traynor
Department of Neuroradiology, Azienda Ospedaliera Città della Salute e della Scienza, Torino, Italy.
Giovanna
G
Carrara
Department of Neuroradiology, Azienda Ospedaliera Città della Salute e della Scienza, Torino, Italy.
Consuelo
C
Valentini
Laboratory of Molecular Genetics, Azienda Ospedaliera Città della Salute e della Scienza, Torino, Italy.
Gabriella
G
Restagno
"Rita Levi Montalcini" Department of Neuroscience, ALS Center, University of Torino, Torino, Italy; Neuroscience Institute of Torino, Torino, Italy. Electronic address: achio@usa.net.
Adriano
A
Chiò
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D013997:Time Factors; D055815:Young Adult
D018389:Codon, Nonsense; D034702:RNA-Binding Protein FUS
Amyotrophic lateral sclerosis; FUS; de novo mutation