학술논문
RCL1copy number variants are associated with a range of neuropsychiatric phenotypes
Document Type
Article
Author
Brownstein, Catherine A.; Smith, Richard S.; Rodan, Lance H.; Gorman, Mark P.; Hojlo, Margaret A.; Garvey, Emily A.; Li, Jianqiao; Cabral, Kristin; Bowen, Joshua J.; Rao, Abhijit S.; Genetti, Casie A.; Carroll, Devon; Deaso, Emma A.; Agrawal, Pankaj B.; Rosenfeld, Jill A.; Bi, Weimin; Howe, Jennifer; Stavropoulos, Dimitri J.; Hansen, Adam W.; Hamoda, Hesham M.; Pinard, Ferne; Caracansi, Annmarie; Walsh, Christopher A.; D’Angelo, Eugene J.; Beggs, Alan H.; Zarrei, Mehdi; Gibbs, Richard A.; Scherer, Stephen W.; Glahn, David C.; Gonzalez-Heydrich, Joseph
Source
Molecular Psychiatry; May 2021, Vol. 26 Issue: 5 p1706-1718, 13p
Subject
Language
ISSN
13594184; 14765578
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 RCL1copy number variations (CNVs) with varying neurodevelopmental or psychiatric phenotypes. These findings suggest that dosage variation of RCL1contributes to a range of neurological and clinical phenotypes.