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NGS study in a sicilian case series with a genetic diagnosis for Gerstmann-Sträussler-Scheinker syndrome (PRNP, p.P102L)

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Abstract

Background

Gerstmann Sträussler Scheinker (GSS) is an inherited, invariably fatal prion disease. Like other human prion diseases, GSS is caused by missense mutations in the prion protein (PrP) gene (PRNP), and by the formation and overtime accumulation of the misfolded, pathogenic scrapie PrP (PrPSc). The first mutation identified in the PRNP gene, and the one blamed as the main cause of the disease, is c.C305T:p.P102L.

Methods and results

The Sanger sequencing method was performed on the PRNP gene for the detection of c.C305T:p.P102L mutations in a cohort of 10 subjects; moreover, a study was carried out, using Next Generation Sequencing (NGS), by sequencing a group of genes related to amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), movement disorders and dementia which show a phenotypic profile similar to that of GSS. The results obtained from the study using NGS indicate the potential role of other genetic variants which could contribute to the various GSS phenotypes.

Conclusions

In conclusion, we highlight the large clinical variability in subjects presenting with GSS and p.P102L, as well as the hypothesis that the mutation in PrP codon 102 alone is not sufficient to trigger the cardinal clinical signs of the disease; furthermore, we do not exclude the possibility that further genetic variants play a decisive role in the aspects of the various phenotypes with which GSS manifests itself.

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Fig. 1

Data Availability

No Data associated in the manuscript.

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Acknowledgements

This study was supported by a grant of the Italian Ministry of Health (RC 2773804) to M.S., M.G.S., F.A.S., and R.F.

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Authors and Affiliations

  1. Oasi Research Institute-IRCCS, Troina, EN, Italy

    Michele Salemi, Maria Grazia Salluzzo, Francesca A. Schillaci, Raffaele Ferri & Corrado Romano

  2. U.O.S. Medical Genetics, Maria Paternò Arezzo Hospital, Ragusa, RG, Italy

    Luana G.M. Mandarà & Concetta Simona Perrotta

  3. Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

    Roberto Castiglione

  4. Genomix4Life Srl, Baronissi, SA, Italy

    Angela Cordella & Roberta Iorio

  5. Genome Research Center for Health-CRGS, Baronissi, SA, Italy

    Angela Cordella & Roberta Iorio

  6. Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy

    Corrado Romano

Authors
  1. Michele Salemi
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  2. Luana G.M. Mandarà
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  3. Maria Grazia Salluzzo
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  4. Francesca A. Schillaci
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  5. Roberto Castiglione
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  6. Angela Cordella
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  7. Roberta Iorio
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  8. Concetta Simona Perrotta
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  9. Raffaele Ferri
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  10. Corrado Romano
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Corresponding author

Correspondence to Michele Salemi.

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All authors declare there is no conflict of interest in this work.

Ethical approval

This study was approved by the Ethical Committee of the Oasi Research Institute-IRCCS, Troina (Italy), (approval number 2022/04/05/CE-IRCCS-OASI/52). All procedures performed in studies involving human participants were following the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Salemi, M., Mandarà, L.G., Salluzzo, M.G. et al. NGS study in a sicilian case series with a genetic diagnosis for Gerstmann-Sträussler-Scheinker syndrome (PRNP, p.P102L). Mol Biol Rep 50, 9715–9720 (2023). https://doi.org/10.1007/s11033-023-08764-z

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  • DOI: https://doi.org/10.1007/s11033-023-08764-z

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