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

TitleRCL1 copy number variants are associated with a range of neuropsychiatric phenotypes.
Publication TypeJournal Article
Year of Publication2021
AuthorsBrownstein, CA, Smith, RS, Rodan, LH, Gorman, MP, Hojlo, MA, Garvey, EA, Li, J, Cabral, K, Bowen, JJ, Rao, AS, Genetti, CA, Carroll, D, Deaso, EA, Agrawal, PB, Rosenfeld, JA, Bi, W, Howe, J, Stavropoulos, DJ, Hansen, AW, Hamoda, HM, Pinard, F, Caracansi, A, Walsh, CA, D'Angelo, EJ, Beggs, AH, Zarrei, M, Gibbs, RA, Scherer, SW, Glahn, DC, Gonzalez-Heydrich, J
JournalMol Psychiatry
Date Published2021 Feb 17

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.

Alternate JournalMol Psychiatry
PubMed ID33597717
Grant ListNA / / BCH | Manton Center for Orphan Disease Research, Boston Children's Hospital (Manton Center for Orphan Disease Research at Boston Children's Hospital) /
NA / / Tommy Fuss Fund /
R01 NS035129 / NS / NINDS NIH HHS / United States
U54 HD090255 / HD / NICHD NIH HHS / United States
K99 NS112604 / NS / NINDS NIH HHS / United States