Novel missense and truncating mutations in FUS/TLS in familial ALS.
BACKGROUND
Mutations in the FUS/TLS gene have been associated with familial amyotrophic lateral sclerosis (FALS).


METHODS
We analyzed the presence and frequency of C-terminal FUS/TLS mutations in a German amyotrophic lateral sclerosis (ALS) cohort, including 133 patients with sporadic ALS (SALS) and 58 patients with FALS by sequence analysis of exons 13-15.


RESULTS
We identified 2 novel heterozygous FUS/TLS mutations in 4 German ALS families including the novel missense mutation K510R and the truncating mutation R495X. The truncating mutation was associated with an aggressive disease course whereas the K510R mutation showed a mild phenotype with disease duration ranging from 6 to 8 years. No mutation was detected in 133 patients with SALS.


CONCLUSIONS
Mutations in FUS/TLS account for 7% (4 of 58) of FALS in our German cohort.
Waibel
S
S
Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany.
Neumann
M
M
Rabe
M
M
Meyer
T
T
Ludolph
A C
AC
D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000235:genetics*; D015331:Cohort Studies; D030541:Databases, Genetic; D005260:Female; D017353:Gene Deletion; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D034702:RNA-Binding Protein FUS / Q000235:genetics*
D034702:RNA-Binding Protein FUS