Absence of TARDBP gene mutations in an italian series of patients with frontotemporal lobar degeneration.
OBJECTIVE
Recent studies showed that TAR DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene, is a major pathological protein in both sporadic and familial frontotemporal lobar degeneration (FTLD). The aim of this study was to search for mutations of the TARDBP gene in the disease.


METHODS
We sequenced the TARDBP gene in 172 unrelated FTLD patients recruited from 2 Italian memory clinics.


RESULTS
We identified 3 different variants of the TARDBP gene in 12 FTLD patients. Three patients showed a silent variant, Ala66Ala (c.332T --> C) in exon 2. A novel heterozygous mutation was found in intron 4 (c.543 + 51A --> G) in 1 patient, which is not located at the splicing site. Finally, a c.208C --> T variant in the 3' untranslated region was detected in 8 probands. None of the aforementioned variants were predicted to affect TDP-43. Hence, pathogenic mutations were not identified in any of the FTLD cases.


CONCLUSIONS
Our study, in accord with previous studies in different populations, found no evidence for a major genetic role of the TARDBP gene in FTLD.
Gallone
Salvatore
S
Neurology II, Department of Neuroscience, University of Turin, Turin, Italy.
Giordana
Maria Teresa
MT
Scarpini
Elio
E
Rainero
Innocenzo
I
Rubino
Elisa
E
Fenoglio
Pierpaola
P
Galimberti
Daniela
D
Grifoni
Silvia
S
Venturelli
Eliana
E
Acutis
Pier Luigi
PL
Peletto
Silvia
S
Maniaci
Maria Grazia
MG
Ferrero
Patrizia
P
Zotta
Michela
M
Pinessi
Lorenzo
L
D000368:Aged; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology
D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D004247:DNA