title: Improving the knowledge of amyotrophic lateral sclerosis genetics: novel SOD1 and FUS variants.
abstract: Amyotrophic lateral sclerosis (ALS) is as an adult-onset neurodegenerative disorder involving both upper and lower motor neurons. About 5% of all cases exhibit signs of frontotemporal degeneration (FTD). We established the mutation frequency of C9ORF72, SOD1, TARDBP, and FUS genes in 307 patients with sporadic ALS, 46 patients with familial ALS (FALS), and 73 patients affected with FTD, all originating from the northeastern part of Italy. C9ORF72 pathogenic expansion was found on 22% of familial ALS, 5% of sporadic ALS, and 14% of FTD patients, resulting the most frequently genetic determinant in our cohort. Sequence analysis of ALS cohort identified 2 novel variants on SOD1 (p.Glu41Gly) and FUS (p.Gly496Glyfs*31). Interestingly, the single base deletion on FUS was observed in an homozygous state, suggesting a recessive pattern of inheritance. No point mutations were identified on FTD cohort. Although useful to direct genetic testing, this study results expand the current knowledge of ALS genetics.
authors: Laboratory of Human Genetics, Department of Biology, University of Padova, Padova, Italy.
authors: Cinzia
authors: C
authors: Bertolin
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Carla
authors: C
authors: D'Ascenzo
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Giorgia
authors: G
authors: Querin
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Alessandra
authors: A
authors: Gaiani
authors: Laboratory of Human Genetics, Department of Biology, University of Padova, Padova, Italy.
authors: Francesca
authors: F
authors: Boaretto
authors: Laboratory of Human Genetics, Department of Biology, University of Padova, Padova, Italy.
authors: Cecilia
authors: C
authors: Salvoro
authors: Laboratory of Human Genetics, Department of Biology, University of Padova, Padova, Italy.
authors: Giovanni
authors: G
authors: Vazza
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Corrado
authors: C
authors: Angelini
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Annachiara
authors: A
authors: Cagnin
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Elena
authors: E
authors: Pegoraro
authors: Department of Neurosciences, University of Padova, Padova, Italy. Electronic address: gianni.soraru@unipd.it.
authors: Gianni
authors: G
authors: Sorarù
authors: Laboratory of Human Genetics, Department of Biology, University of Padova, Padova, Italy. Electronic address: marialuisa.mostacciuolo@unipd.it.
authors: Maria Luisa
authors: ML
authors: Mostacciuolo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000073885:C9orf72 Protein; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D011506:Proteins / Q000235:genetics; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D055815:Young Adult
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D004268:DNA-Binding Proteins; D011506:Proteins; D034702:RNA-Binding Protein FUS; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: ALS; C9ORF72; FTD; FUS; Genetic screening; SOD1; TARDBP