Molecular psychiatry · 2021
RCL1 copy number variants are associated with a range of neuropsychiatric phenotypes.
Клинический случайСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.