A Customized Next-Generation Sequencing-Based Panel to Identify Novel Genetic Variants in Dementing Disorders: A...

Area of Science:

• Neurogenetics
• Genomics
• Molecular Biology

Background:

• Next-generation sequencing (NGS) enables efficient genetic variant detection.
• Current clinical sequencing often focuses on targeted gene panels for specific diseases.

Purpose of the Study:

• To screen 16 genes using a custom NGS panel in 8 patients with various neurodegenerative cognitive disorders.
• To evaluate the utility of a targeted NGS approach for identifying disease-associated genetic variants.

Main Methods:

• A custom NGS gene panel was designed and utilized.
• 16 genes were screened in 8 patients with Alzheimer's disease, mild cognitive impairment, frontotemporal dementia, and dementia associated with Parkinson's disease.
• Variant pathogenicity was assessed using American College of Medical Genetics (ACMG) guidelines.

Main Results:

• Pathogenic or likely pathogenic variants in TREM2 and APP genes were identified in three patients.
• A likely pathogenic variant (p.R205W) in the CHMP2B gene was found in one patient.
• Likely pathogenic variants were also identified in the GRN and APP genes, while variants in CSF1R and SERPINI1 were classified as benign.

Conclusions:

• The study detected rare genetic variants potentially associated with neurodegenerative disorders.
• While preliminary, this NGS-based approach offers promising translational perspectives for diagnosis and management.
• Further research and replication are needed to validate these findings and advance clinical applications.