RCL1 copy number variants are associated with a range of neuropsychiatric phenotypes
Catherine A Brownstein1,2,3,4,5, Richard S Smith6,7,8,9,10, Lance H Rodan6,11
1Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA. Catherine.brownstein@childrens.harvard.edu.
Molecular Psychiatry
|February 18, 2021
Summary
Genetic variations in the RCL1 gene are linked to severe early-onset psychiatric conditions. Dosage variations of this gene contribute to diverse neurological and clinical phenotypes, offering insights for early interventions.
Area of Science:
- Genetics
- Neuroscience
- Psychiatry
Background:
- Mendelian and early-onset severe psychiatric phenotypes are often associated with large-effect genetic variants.
- Identifying these variants can facilitate genetic discoveries and early therapeutic interventions.
Observation:
- An 18-year-old male experienced cognitive decline starting at age 14, followed by catatonia, hallucinations, paranoia, aggression, mood dysregulation, and disorganized thoughts.
- Exome sequencing identified a stop-gain mutation in the highly conserved RCL1 gene (NM_005772.4:c.370C>T, p.Gln124Ter).
Findings:
- The mutation affects the RNA 3'-terminal phosphate cyclase-like protein encoded by RCL1.
- Further investigation revealed eleven additional cases with RCL1 copy number variations (CNVs) presenting with diverse neurodevelopmental or psychiatric phenotypes.
Implications:
- Dosage variations in the RCL1 gene are implicated in a spectrum of neurological and clinical disorders.
- These findings highlight RCL1 as a potential target for understanding and treating severe psychiatric and neurodevelopmental conditions.
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