RCL1 copy number variants are associated with a range of neuropsychiatric phenotypes

Catherine A. Brownstein, Richard S. Smith, Lance H. Rodan, Mark P. Gorman, Margaret A. Hojlo, Emily A. Garvey, Jianqiao Li, Kristin Cabral, Joshua J. Bowen, Abhijit S. Rao, Casie A. Genetti, Devon Carroll, Emma A. Deaso, Pankaj B. Agrawal, Jill A. Rosenfeld, Weimin Bi, Jennifer Howe, Dimitri J. Stavropoulos, Adam W. Hansen, Hesham M. HamodaFerne Pinard, Annmarie Caracansi, Christopher A. Walsh, Eugene J. D’Angelo, Alan H. Beggs, Mehdi Zarrei, Richard A. Gibbs, Stephen W. Scherer, David C. Glahn, Joseph Gonzalez-Heydrich

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Mendelian and early-onset severe psychiatric phenotypes often involve genetic variants having a large effect, offering opportunities for genetic discoveries and early therapeutic interventions. Here, the index case is an 18-year-old boy, who at 14 years of age had a decline in cognitive functioning over the course of a year and subsequently presented with catatonia, auditory and visual hallucinations, paranoia, aggression, mood dysregulation, and disorganized thoughts. Exome sequencing revealed a stop-gain mutation in RCL1 (NM_005772.4:c.370 C > T, p.Gln124Ter), encoding an RNA 3′-terminal phosphate cyclase-like protein that is highly conserved across eukaryotic species. Subsequent investigations across two academic medical centers identified eleven additional cases of RCL1 copy number variations (CNVs) with varying neurodevelopmental or psychiatric phenotypes. These findings suggest that dosage variation of RCL1 contributes to a range of neurological and clinical phenotypes.

Original languageEnglish (US)
Pages (from-to)1706-1718
Number of pages13
JournalMolecular psychiatry
Volume26
Issue number5
DOIs
StatePublished - May 2021
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

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