High frequency of TARDBP gene mutations in italian patients with amyotrophic lateral sclerosis

Lucia Corrado, A. Ratti, C. Gellera, E. Buratti, B. Castellotti, Y. Carlomagno, N. Ticozzi, L. Mazzini, L. Testa, F. Taroni, F. E. Baralle, V. Silani, S. D'Alfonso

Research output: Contribution to journalArticle

Abstract

Recent studies identified rare missense mutations in amyotrophic lateral sclerosis (ALS) patients in the TARDBP gene encoding TAR DNA binding protein (TDP)-43, the major protein of the ubiquitinated inclusions (UBIs) found in affected motor neurons (MNs). The aim of this study was to further define the spectrum of TARDBP mutations in a large cohort of 666 Italian ALS patients (125 familial and 541 sporadic cases). The entire coding region was sequenced in 281 patients, while in the remaining 385 cases only exon 6 was sequenced. In 18 patients, of which six are familial, we identified 12 different heterozygous missense mutations (nine novel) all locating to exon 6, which were absent in 771 matched controls. The c.1144G

Original languageEnglish
Pages (from-to)688-694
Number of pages7
JournalHuman Mutation
Volume30
Issue number4
DOIs
Publication statusPublished - 2009

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Keywords

  • ALS
  • Amyotrophic lateral sclerosis
  • Frontotemporal dementia
  • Lymphocytes
  • Motor neurons
  • Mutations
  • TARDBP
  • TDP-43

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Corrado, L., Ratti, A., Gellera, C., Buratti, E., Castellotti, B., Carlomagno, Y., Ticozzi, N., Mazzini, L., Testa, L., Taroni, F., Baralle, F. E., Silani, V., & D'Alfonso, S. (2009). High frequency of TARDBP gene mutations in italian patients with amyotrophic lateral sclerosis. Human Mutation, 30(4), 688-694. https://doi.org/10.1002/humu.20950