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. Conclusion: Our study, in accord with previous studies in different populations, found no evidence for a major genetic role of the TARDBP gene in FTLD.

Absence of TARDBP Gene Mutations in an Italian Series of Patients with Frontotemporal Lobar Degeneration

GIORDANA, Maria Teresa;RAINERO, Innocenzo;RUBINO, Elisa;GRIFONI, Silvia;PINESSI, Lorenzo
2009

Abstract

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. Conclusion: Our study, in accord with previous studies in different populations, found no evidence for a major genetic role of the TARDBP gene in FTLD.
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http://dx.doi.org/10.1159/000241876
TDP-43; genetics; FTLD
Salvatore Gallone; Maria Teresa Giordana; Elio Scarpini; Innocenzo Rainero; Elisa Rubino; Pierpaola Fenoglio; Daniela Galimberti; Silvia Grifoni; Eliana Venturelli; Pier Luigi Acutis; Silvia Peletto; Maria Grazia Maniaci; Patrizia Ferrero; Michela Zotta; Lorenzo Pinessi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/62376
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