EXPLORATORY ANALYSIS OF RARE AND NOVEL VARIANTS IN MEXICAN PATIENTS DIAGNOSED WITH SCHIZOPHRENIA AND DEMENTIA

Rev Invest Clin. 2019;71(4):246-254. doi: 10.24875/RIC.19002923.

Abstract

Background: Schizophrenia (SCZ) and dementia, often related, are two of the most common neuropsychiatric diseases; epidemiological studies have shown that SCZ patients present a 2-fold increased risk for dementia compared to non-schizophrenic individuals. We explored the presence of rare and novel damaging gene variants in patients diagnosed with late-onset dementia of Alzheimer's type (DAT) or SCZ.

Methods: We included 7 DAT and 12 SCZ patients and performed high-depth targeted sequencing of 184 genes.

Results: We found novel and rare damaging variants in 18 genes in these Mexican patients. Carriers of these variants showed extreme phenotypes, including, treatment-resistant SCZ or cognitive decline. Furthermore, we found a variation on ABCC1 as a possible link between psychosis and cognitive impairment.

Discussion: As an exploratory analysis, we report some interesting variations that should be corroborated in larger sample size studies.

Keywords: Dementia; Next-generation sequencing; Novel variants; Rare variants; Schizophrenia.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology*
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / physiopathology*
  • Dementia / genetics
  • Dementia / physiopathology*
  • Genetic Variation
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mexico
  • Multidrug Resistance-Associated Proteins / genetics
  • Phenotype
  • Schizophrenia / genetics
  • Schizophrenia / physiopathology*

Substances

  • Multidrug Resistance-Associated Proteins
  • multidrug resistance-associated protein 1