preprints.org > biology and life sciences > biochemistry and molecular biology > doi: 10.20944/preprints201909.0346.v1

Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 28 September 2019 / Approved: 30 September 2019 / Online: 30 September 2019 (11:05:36 CEST)

Background: Advancements in the next-generation sequencing (NGS) techniques have allowed for efficient genetic variant detection at reduced costs. Methods: We describe an ad hoc NGS-based custom designed resequencing gene panel to identify genetic variants in 8 patients with dementing disorders. Results: We found variants of TREM2 and APP genes in three patients; these have been previously identified as pathogenic or likely pathogenic and, therefore, considered as “Disease Causing”. In the remaining subjects, the pathogenicity was evaluated on the in silico analysis, according to the guidelines of the American College of Medical Genetics. In one patient, the p.R205W variant was causative of the disease, thus considered as “Possibly Disease Causing”. The variants found from the other four subjects in the CSF1R, SERPINI1, GRN, and APP genes revealed discordant in silico results and, therefore, it was not possible to assign a definitive pathogenicity. Conclusions: Notwithstanding the limitations of a customized panel, we detected some rare genetic variants with a probable disease association. The future application of NGS techniques and the further replication of these experimental data will replace the so-called “gene by gene” approach with a “panel of genes” strategy, that offers promising perspectives in the diagnosis and management of neurodegenerative disorders.

neurogenetics; dementia; next-generation sequencing; in silico analysis; genetic variant; phenotypic variability

Biology and Life Sciences, Biochemistry and Molecular Biology

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