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Basic Science and Pathogenesis.

Vorapun Senanarong1,2, Chatchawan Rattanabannakit2, Natthamon Wongkom3

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Summary
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This study identified genetic variants in Thai patients with early-onset dementia (EOD) and familial dementia using next-generation sequencing. Findings aid in diagnosing EOD and understanding its genetic causes.

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Area of Science:

  • Genetics
  • Neurology
  • Molecular Biology

Background:

  • Early-onset dementia (EOD) affects individuals before age 65, presenting diagnostic challenges due to genetic and clinical heterogeneity.
  • Limited genetic studies on EOD exist for the Thai population.
  • Investigating the genetic underpinnings of EOD is crucial for accurate diagnosis and treatment.

Purpose of the Study:

  • To determine the genetic spectrum of early-onset dementia (EOD) in Thai patients.
  • To analyze the genetic profiles of individuals with a family history of dementia.
  • To identify pathogenic variants contributing to EOD in the Thai population.

Main Methods:

  • Recruited 150 subjects with EOD and 18 with familial dementia.
  • Conducted targeted next-generation sequencing (NGS) on 38 dementia-associated genes.
  • Analyzed genetic variants, including pathogenic and variants of uncertain significance (VUS).

Main Results:

  • Identified pathogenic variants in 15 subjects (10% of the cohort).
  • PSEN1 variants were most frequent (33.33%), including a novel variant (c.817G>A, p.Glu273Lys).
  • 61 subjects had variants of uncertain significance (VUS), highlighting genetic complexity.

Conclusions:

  • The study elucidates the genetic landscape of EOD and familial dementia in Thai patients.
  • Next-generation sequencing is effective in identifying genetic causes of dementia, including Alzheimer's disease.
  • Genetic testing for known causal genes aids in precise EOD diagnosis.