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.
Neurology II, Department of Neuroscience, University of Turin, Turin, Italy.
Salvatore
S
Gallone
Maria Teresa
MT
Giordana
Elio
E
Scarpini
Innocenzo
I
Rainero
Elisa
E
Rubino
Pierpaola
P
Fenoglio
Daniela
D
Galimberti
Silvia
S
Grifoni
Eliana
E
Venturelli
Pier Luigi
PL
Acutis
Silvia
S
Peletto
Maria Grazia
MG
Maniaci
Patrizia
P
Ferrero
Michela
M
Zotta
Lorenzo
L
Pinessi
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