Progranulin mutations and amyotrophic lateral sclerosis or amyotrophic lateral sclerosis-frontotemporal dementia phenotypes.
OBJECTIVE
Mutations in the progranulin (PGRN) gene were recently described as the cause of ubiquitin positive frontotemporal dementia (FTD). Clinical and pathological overlap between amyotrophic lateral sclerosis (ALS) and FTD prompted us to screen PGRN in patients with ALS and ALS-FTD.


METHODS
The PGRN gene was sequenced in 272 cases of sporadic ALS, 40 cases of familial ALS and in 49 patients with ALS-FTD.


RESULTS
Missense changes were identified in an ALS-FTD patient (p.S120Y) and in a single case of limb onset sporadic ALS (p.T182M), although the pathogenicity of these variants remains unclear.


CONCLUSIONS
PGRN mutations are not a common cause of ALS phenotypes.
Schymick
J C
JC
Laboratory of Neurogenetics, National Institute of Aging, NIH, Bethesda, Maryland, USA.
Yang
Y
Y
Andersen
P M
PM
Vonsattel
J P
JP
Greenway
M
M
Momeni
P
P
Elder
J
J
Chiò
A
A
Restagno
G
G
Robberecht
W
W
Dahlberg
C
C
Mukherjee
O
O
Goate
A
A
Graff-Radford
N
N
Caselli
R J
RJ
Hutton
M
M
Gass
J
J
Cannon
A
A
Rademakers
R
R
Singleton
A B
AB
Hardiman
O
O
Rothstein
J
J
Hardy
J
J
Traynor
B J
BJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications* / Q000235:genetics*; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D003704:Dementia / Q000209:etiology* / Q000235:genetics*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D000077153:Progranulins
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins