title: Familial ALS with FUS P525L mutation: two Japanese sisters with multiple systems involvement.
abstract: We evaluated the clinicopathological features of familial amyotrophic lateral sclerosis (ALS) with the fused in sarcoma (FUS) P525L mutation. Two sisters and their mother had a similar clinical course, which was characterized by the development of limb weakness at a young age with rapid disease progression. An elder sister, patient 1, progressed into a totally locked-in state requiring mechanical ventilation and died 26 years after the onset of the disease. In contrast, the younger sister, patient 2, died in the early stages of the disease. The patients had neuropathological findings that indicated a very active degeneration of motor neurons and multiple system degeneration, which led to marked brain and spinal cord atrophy in the long term clinical outcome. The multiple system degeneration included the frontal lobe, the basal ganglia and substantia nigra, cerebellum and related area. Compared with previously reported ALS cases, the severe degeneration of the frontal lobe and the striatum were the characteristic features in the patient 1 in this case study. The degeneration spread over multiple systems might be caused not only by the appearance of the FUS immunoreactive neuronal cytoplasmic inclusions but also by the degeneration of neuronal connections from the primary motor cortex and related areas.
authors.affiliation: Department of Pathology, Tokyo Metropolitan Neurological Hospital, Tokyo 183-0042, Japan. mochi@nihon-u.ne.jp
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mochizuki
authors.forename: Eiji
authors.initials: E
authors.lastname: Isozaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Takao
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibuya
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.forename: Masato
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Akihito
authors.initials: A
authors.lastname: Kawata
authors.forename: Kiyomitsu
authors.initials: K
authors.lastname: Oyanagi
authors.forename: Ban
authors.initials: B
authors.lastname: Mihara
authors.forename: Toshio
authors.initials: T
authors.lastname: Mizutani
mesh_terms: D000328:Adult; D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000145:classification / Q000150:complications / Q000235:genetics* / Q000473:pathology; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D010244:Bulbar Palsy, Progressive / Q000209:etiology / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D005911:Gliosis / Q000209:etiology / Q000473:pathology; D006801:Humans; D002479:Inclusion Bodies / Q000648:ultrastructure; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000032:analysis; D017354:Point Mutation; D011782:Quadriplegia / Q000209:etiology; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000209:etiology / Q000628:therapy; D013116:Spinal Cord / Q000473:pathology*; D013194:Staining and Labeling
chemical_list: D009419:Nerve Tissue Proteins; D034702:RNA-Binding Protein FUS