title: Sporadic juvenile amyotrophic lateral sclerosis caused by mutant FUS/TLS: possible association of mental retardation with this mutation.
abstract: We present two cases of patients with juvenile amyotrophic lateral sclerosis (ALS), who had no history of familial ALS. The symptoms of both patients started as weakness of the unilateral upper limb and neck, and extended to bulbar and respiratory weakness in a relatively short period. Of note, the first patient was mentally retarded before the onset of weakness. Fused in sarcoma/translocated in liposarcoma (FUS/TLS) gene analyses revealed mutations of p. G492EfsX527 (c. 1475delG), which is a novel deletion/frameshift mutation, in the first patient and p. R514S mutation (c. 1542G > T) in the second patient. Molecular analysis revealed that the mutant FUS/TLS, especially the deletion/frameshift mutation, showed significant cytoplasmic localization in transfected motor neuron-like cells. Our findings suggest the association of mental retardation with the FUS/TLS mutation. Further investigation, including the effect of FUS/TLS on cognitive function, would aid better understanding of FUS/TLS proteinopathies.
authors: Department of Neurology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. y-stsh@kumamoto-u.ac.jp
authors: Satoshi
authors: S
authors: Yamashita
authors: Akira
authors: A
authors: Mori
authors: Hideya
authors: H
authors: Sakaguchi
authors: Tomohiro
authors: T
authors: Suga
authors: Daijirou
authors: D
authors: Ishihara
authors: Akihiko
authors: A
authors: Ueda
authors: Taro
authors: T
authors: Yamashita
authors: Yasushi
authors: Y
authors: Maeda
authors: Makoto
authors: M
authors: Uchino
authors: Teruyuki
authors: T
authors: Hirano
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D055815:Young Adult
chemical_list: D034702:RNA-Binding Protein FUS