title: De novo FUS mutations in 2 Korean patients with sporadic amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder. Approximately 5% of ALS patients are familial (fALS) cases, and the remaining 95% are apparently sporadic (sALS) cases. To date, a number of genes have been discovered as associated with ALS, but the genetic background of sALS is not yet fully understood. The occurrence of de novo mutations in ALS genes might be an explanation for sALS, but reduced penetrance could be an alternative theory. Previously, we screened mutations in 5 ALS genes including SOD1 and FUS in 9 fALS and 249 sALS patients and found a total of 15 patients with either SOD1 (7 fALS and 3 sALS) or FUS (1 fALS and 4 sALS) mutations. Interestingly, only 1 fALS patient had the FUS mutation, whereas 4 sALS patients had mutations in this gene. To determine if the FUS mutations in sALS were de novo, we performed genetic analysis on 2 sALS patients with living parents. Genetic analysis confirmed that 2 FUS mutations, including the c.1483C>T (p.Arg495*) and the c.1509_1510delAG (p.Gly504Trpfs*12) mutations, were found only in the patients and not in their parents, confirming the de novo occurrence of these mutations. These findings support the notion that de novo mutations are responsible for a certain proportion of sALS.
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Kim
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea; Cell Therapy Center, Hanyang University Hospital, Seoul, Republic of Korea.
authors.forename: Ki-Wook
authors.initials: KW
authors.lastname: Oh
authors.affiliation: Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea; Cell Therapy Center, Hanyang University Hospital, Seoul, Republic of Korea.
authors.forename: Won-Jun
authors.initials: WJ
authors.lastname: Choi
authors.affiliation: Cell Therapy Center, Hanyang University Hospital, Seoul, Republic of Korea; Department of Neurology, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Seong-il
authors.initials: SI
authors.lastname: Oh
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: changski@skku.edu.
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea; Cell Therapy Center, Hanyang University Hospital, Seoul, Republic of Korea. Electronic address: kimsh1@hanyang.ac.kr.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007723:Korea; D008297:Male; D009154:Mutation / Q000235:genetics*; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D055815:Young Adult
chemical_list: C000599550:FUS protein, human; D034702:RNA-Binding Protein FUS
keywords: Amyotrophic lateral sclerosis; De novo mutation; FUS