title: Two Italian kindreds with familial amyotrophic lateral sclerosis due to FUS mutation.
abstract: Recently, fused in sarcoma/translated in liposarcoma (FUS/TLS) gene, located on chromosome 16p11.2, has been identified as a disease gene in familial amyotrophic lateral sclerosis (FALS). We have analyzed FUS/TLS in a cohort of 52 index cases from seven Italian regions with non-SOD1 and non-TARDBP FALS. We identified a heterozygous c.G1542C missense mutation in a family of northern Italian origin, and a heterozygous c.C1574T missense mutation in a family of Sicilian origin. Both variants are located in exon 15 encoding the RNA-recognition motif, and result in a substitution of an arginine with a serine in position 514 (p.R514S) and substitution of a proline with a leucine at position 525 (p.P525L), respectively. Overall, the two mutations accounted for 3.8% of 52 non-SOD1 and non-TDP43 index cases of FALS. The clinical phenotype was similar within each of the families, with a predominantly upper limb onset in the family carrying the p.R514S mutation and bulbar onset, with very young age and a rapid course in the family carrying the p.P525L mutation.
authors.affiliation: ALS Center, Department of Neuroscience, University of Turin, Turin, Italy. achio@usa.net
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.forename: Gabriella
authors.initials: G
authors.lastname: Restagno
authors.forename: Maura
authors.initials: M
authors.lastname: Brunetti
authors.forename: Irene
authors.initials: I
authors.lastname: Ossola
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mora
authors.forename: Mario
authors.initials: M
authors.lastname: Sabatelli
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Monsurrò
authors.forename: Stefania
authors.initials: S
authors.lastname: Battistini
authors.forename: Jessica
authors.initials: J
authors.lastname: Mandrioli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Salvi
authors.forename: Rossella
authors.initials: R
authors.lastname: Spataro
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schymick
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
authors.forename: Vincenzo
authors.initials: V
authors.lastname: La Bella
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005190:Family; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D055815:Young Adult
chemical_list: D034702:RNA-Binding Protein FUS