NGS Study in a Sicilian Case Series with a Genetic Diagnosis for Gerstmann-Sträussler-Scheinker Syndrome (PRNP, P.P102L)

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2023 Oct 9

PMID 37812352

Authors

Michele Salemi

Luana G M Mandara

Maria Grazia Salluzzo

Francesca A Schillaci

Roberto Castiglione

Angela Cordella

Roberta Iorio

Concetta Simona Perrotta

Raffaele Ferri

Corrado Romano

Affiliations

Soon will be listed here.

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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