Frontiers in Genetics (Apr 2021)

Familial Psychosis Associated With a Missense Mutation at MACF1 Gene Combined With the Rare Duplications DUP3p26.3 and DUP16q23.3, Affecting the CNTN6 and CDH13 Genes

  • Josep Pol-Fuster,
  • Josep Pol-Fuster,
  • Francesca Cañellas,
  • Francesca Cañellas,
  • Laura Ruiz-Guerra,
  • Laura Ruiz-Guerra,
  • Aina Medina-Dols,
  • Aina Medina-Dols,
  • Bàrbara Bisbal-Carrió,
  • Bàrbara Bisbal-Carrió,
  • Víctor Asensio,
  • Víctor Asensio,
  • Bernat Ortega-Vila,
  • Bernat Ortega-Vila,
  • Diego Marzese,
  • Diego Marzese,
  • Carme Vidal,
  • Carmen Santos,
  • Jerònia Lladó,
  • Jerònia Lladó,
  • Gabriel Olmos,
  • Gabriel Olmos,
  • Damià Heine-Suñer,
  • Damià Heine-Suñer,
  • Konstantin Strauch,
  • Konstantin Strauch,
  • Antònia Flaquer,
  • Antònia Flaquer,
  • Cristòfol Vives-Bauzà,
  • Cristòfol Vives-Bauzà,
  • Cristòfol Vives-Bauzà

DOI
https://doi.org/10.3389/fgene.2021.622886
Journal volume & issue
Vol. 12

Abstract

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Psychosis is a highly heritable and heterogeneous psychiatric condition. Its genetic architecture is thought to be the result of the joint effect of common and rare variants. Families with high prevalence are an interesting approach to shed light on the rare variant’s contribution without the need of collecting large cohorts. To unravel the genomic architecture of a family enriched for psychosis, with four affected individuals, we applied a system genomic approach based on karyotyping, genotyping by whole-exome sequencing to search for rare single nucleotide variants (SNVs) and SNP array to search for copy-number variants (CNVs). We identified a rare non-synonymous variant, g.39914279 C > G, in the MACF1 gene, segregating with psychosis. Rare variants in the MACF1 gene have been previously detected in SCZ patients. Besides, two rare CNVs, DUP3p26.3 and DUP16q23.3, were also identified in the family affecting relevant genes (CNTN6 and CDH13, respectively). We hypothesize that the co-segregation of these duplications with the rare variant g.39914279 C > G of MACF1 gene precipitated with schizophrenia and schizoaffective disorder.

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