Two Italian kindreds with familial amyotrophic lateral sclerosis due to FUS mutation.
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.
Chiò
Adriano
A
ALS Center, Department of Neuroscience, University of Turin, Turin, Italy. achio@usa.net
Restagno
Gabriella
G
Brunetti
Maura
M
Ossola
Irene
I
Calvo
Andrea
A
Mora
Gabriele
G
Sabatelli
Mario
M
Monsurrò
Maria Rosaria
MR
Battistini
Stefania
S
Mandrioli
Jessica
J
Salvi
Fabrizio
F
Spataro
Rossella
R
Schymick
Jennifer
J
Traynor
Bryan J
BJ
La Bella
Vincenzo
V
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
D034702:RNA-Binding Protein FUS