Genotype-Driven Diagnosis Enables Targeted Pharmacological Treatment in Brunner Syndrome: A Novel Splice-Site MAOA Variant and Case-Based Review.
Level 4 - case-series / case-control
Single-patient clinical case report with functional molecular validation and literature review.
PubMed 42511567 · doi:10.3390/ijms27146223
What was done
Clinical exome sequencing was performed in a patient presenting with intellectual disability and no family history of neurodevelopmental disorder after first-line diagnostic approaches were negative. Patient-derived mRNA was functionally analyzed to determine the splicing impact of the identified variant, and the patient was treated with an off-label serotonin antagonist and reuptake inhibitor (SARI) alongside a case-based review of MAOA deficiency.
What was found
Sequencing identified a novel splice-site variant in the MAOA gene, with mRNA analysis confirming intron 8 retention leading to a premature stop codon (loss-of-function mechanism). SARI treatment was associated with improvement in social behavior and sleep disturbances. The abstract reports no numerical outcome measures, effect sizes, or quantitative scores.
Why it matters
This report broadens the known mutational spectrum for Brunner syndrome and presents the first reported use of SARI-class pharmacotherapy as a potential personalized treatment for monoamine-driven behavioral and sleep symptoms in MAOA deficiency.
Limits
Evidence is limited to a single uncontrolled, unblinded patient (n = 1). The abstract provides no quantitative clinical metrics, control comparison, duration of follow-up, or systematic assessment of potential adverse effects.
Cited by
- supports MAOA is an enzyme that degrades monoamines which regulate neuronal communication.