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 May
KeywordsAdolescent, DNA Copy Number Variations, Exome Sequencing, Humans, Male, Mutation, Phenotype

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
PubMed Central IDPMC8159744
Grant ListR01 NS035129 / NS / NINDS NIH HHS / United States
U54 HD090255 / HD / NICHD NIH HHS / United States
K99 NS112604 / NS / NINDS NIH HHS / United States
/ / CIHR / Canada

Similar Publications

Chen F, Zhang Y, Chandrashekar DS, Varambally S, Creighton CJ. Global impact of somatic structural variation on the cancer proteome. Nat Commun. 2023;14(1):5637.
Rhie A, Nurk S, Cechova M, Hoyt SJ, Taylor DJ, Altemose N, et al.. The complete sequence of a human Y chromosome. Nature. 2023;621(7978):344-354.
Saengboonmee C, Sorin S, Sangkhamanon S, Chomphoo S, Indramanee S, Seubwai W, et al.. γ-aminobutyric acid B2 receptor: A potential therapeutic target for cholangiocarcinoma in patients with diabetes mellitus. World J Gastroenterol. 2023;29(28):4416-4432.
Wojcik MH, Reuter CM, Marwaha S, Mahmoud M, Duyzend MH, Barseghyan H, et al.. Beyond the exome: What's next in diagnostic testing for Mendelian conditions. Am J Hum Genet. 2023;110(8):1229-1248.
Chin C-S, Behera S, Khalak A, Sedlazeck FJ, Sudmant PH, Wagner J, et al.. Multiscale analysis of pangenomes enables improved representation of genomic diversity for repetitive and clinically relevant genes. Nat Methods. 2023;20(8):1213-1221.
Zhao N, Teles F, Lu J, Koestler DC, Beck J, Boerwinkle E, et al.. Epigenome-wide association study using peripheral blood leukocytes identifies genomic regions associated with periodontal disease and edentulism in the Atherosclerosis Risk in Communities study. J Clin Periodontol. 2023;50(9):1140-1153.
Harris RA, McAllister JM, Strauss JF. Single-Cell RNA-Seq Identifies Pathways and Genes Contributing to the Hyperandrogenemia Associated with Polycystic Ovary Syndrome. Int J Mol Sci. 2023;24(13).
Qian X, Srinivasan T, He J, Chen R. The Role of Ceramide in Inherited Retinal Disease Pathology. Adv Exp Med Biol. 2023;1415:303-307.
Calame DG, Guo T, Wang C, Garrett L, Jolly A, Dawood M, et al.. Monoallelic variation in DHX9, the gene encoding the DExH-box helicase DHX9, underlies neurodevelopment disorders and Charcot-Marie-Tooth disease. Am J Hum Genet. 2023;110(8):1394-1413.
Walker KA, Chen J, Shi L, Yang Y, Fornage M, Zhou L, et al.. Proteomics analysis of plasma from middle-aged adults identifies protein markers of dementia risk in later life. Sci Transl Med. 2023;15(705):eadf5681.