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

Autor: Brownstein CA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA. Catherine.brownstein@childrens.harvard.edu.; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA. Catherine.brownstein@childrens.harvard.edu.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Catherine.brownstein@childrens.harvard.edu.; Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, USA. Catherine.brownstein@childrens.harvard.edu.; EPICenter, Boston Children's Hospital, Boston, MA, USA. Catherine.brownstein@childrens.harvard.edu., Smith RS; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.; Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, USA.; EPICenter, Boston Children's Hospital, Boston, MA, USA., Rodan LH; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.; Department of Neurology, Boston Children's Hospital, Boston, MA, USA., Gorman MP; Department of Neurology, Boston Children's Hospital, Boston, MA, USA., Hojlo MA; Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, USA.; EPICenter, Boston Children's Hospital, Boston, MA, USA.; Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA, USA., Garvey EA; Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, USA.; EPICenter, Boston Children's Hospital, Boston, MA, USA.; Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA, USA., Li J; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA., Cabral K; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA., Bowen JJ; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA., Rao AS; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.; Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, USA.; Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA, USA., Genetti CA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA., Carroll D; Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, USA.; Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA, USA., Deaso EA; Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, USA.; EPICenter, Boston Children's Hospital, Boston, MA, USA.; Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA, USA., Agrawal PB; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.; Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA., Rosenfeld JA; Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA.; Baylor Genetics Laboratories, Houston, TX, USA., Bi W; Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA.; Baylor Genetics Laboratories, Houston, TX, USA., Howe J; The Centre for Applied Genomics and Programs in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada., Stavropoulos DJ; Genome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada., Hansen AW; Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA.; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA., Hamoda HM; Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA, USA., Pinard F; Department of Neurology, Boston Children's Hospital, Boston, MA, USA., Caracansi A; Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA, USA., Walsh CA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., D'Angelo EJ; Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, USA.; Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA, USA.; Department of Psychiatry, Harvard Medical School, Boston, MA, USA., Beggs AH; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Zarrei M; The Centre for Applied Genomics and Programs in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada., Gibbs RA; Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA.; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA., Scherer SW; The Centre for Applied Genomics and Programs in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.; Department of Molecular Genetics and McLaughlin Centre, University of Toronto, Toronto, ON, Canada., Glahn DC; Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, USA.; EPICenter, Boston Children's Hospital, Boston, MA, USA.; Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA, USA.; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.; Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA., Gonzalez-Heydrich J; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.; Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, USA.; EPICenter, Boston Children's Hospital, Boston, MA, USA.; Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA, USA.; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2021 May; Vol. 26 (5), pp. 1706-1718. Date of Electronic Publication: 2021 Feb 17.
DOI: 10.1038/s41380-021-01035-y
Abstrakt: 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.
Databáze: MEDLINE