Neurological Sciences

, Volume 40, Issue 10, pp 2111–2118 | Cite as

A novel S379A TARDBP mutation associated to late-onset sporadic ALS

  • Teresa Sprovieri
  • Carmine UngaroEmail author
  • Benedetta Perrone
  • Giuseppina Daniela Naimo
  • Rossella Spataro
  • Sebastiano Cavallaro
  • Vincenzo La Bella
  • Francesca Luisa Conforti
Original Article


Since 2008, several groups have reported a lot of dominant mutations in TARDBP gene as a primary cause of Amyotrophic lateral sclerosis (ALS). Mutations in TARDBP gene are responsible for 4–5% of familial ALS (fALS) and nearly 1% of sporadic ALS (sALS). To date, over 50 dominant mutations were found in TDP-43 in both familial and sporadic ALS patients, most of which were missense mutations in the C-terminal glycine-rich region. Herein, we describe the clinical and genetic analysis of an Italian non-familial ALS patient with a late onset and a rapid disease progression, which led to the discovery of a novel TARDBP mutation. After neurological evaluation, molecular investigation highlighted the heterozygous substitution in exon 6 of TARDBP gene (S379A), which has previously neither been described nor reported in the ALS database. Several evidences supported the S379A mutation as causative in our patient: (a) it was neither found in ExAC nor 1000G and it was absent in our database of control subjects; (b) the position of the mutation involves an evolutionarily highly conserved residue; (c) two different amino acid substitutions in the same 379 codon were already reported in Swedish and Italian fALS cases, supporting the critical role of this codon for the protein function. The identification of this novel mutation enlarges the number of TARDBP mutations in ALS patients.


ALS TARDBP TDP-43 Mutation 



The authors gratefully acknowledge Ariangela Belvedere, Walter Carpino, Benedetto Bruno, Patrizia Rizzuto, Tiziana Martire, and Angelo Bagalà for their administrative and technical support.

Authors’ contributions

Analysis, acquisition, and interpretation of data: CU, TS, BP, and GDN. Provision of patient samples and collection of clinical data: RS and VLB. Drafting and revising of manuscript: FLC, CU, TS, SB, VLB. Study conception and design: FLC.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all patients.


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Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  • Teresa Sprovieri
    • 1
  • Carmine Ungaro
    • 1
    Email author
  • Benedetta Perrone
    • 1
  • Giuseppina Daniela Naimo
    • 1
  • Rossella Spataro
    • 2
  • Sebastiano Cavallaro
    • 1
  • Vincenzo La Bella
    • 3
  • Francesca Luisa Conforti
    • 4
  1. 1.Institute of Neurological SciencesNational Research CouncilMangoneItaly
  2. 2.IRCCS Centro Neurolesi “Bonino Pulejo”PalermoItaly
  3. 3.ALS Clinical Research Center and Laboratory of Neurochemistry, Department of Experimental Biomedicine and Clinical NeurosciencesUniversity of PalermoPalermoItaly
  4. 4.Department of Pharmacy and Health and Nutritional SciencesUniversity of CalabriaRendeItaly

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