Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A.
Level 4 - case-series / case-control
Family pedigree and genetic case series of a single kindred.
PubMed 8211186 · doi:10.1126/science.8211186
What was done
Genetic and metabolic analyses were conducted on a single large kindred containing multiple males with borderline mental retardation and abnormal behaviors, including impulsive aggression, arson, attempted rape, and exhibitionism. The investigators evaluated 24-hour urine samples for monoamine metabolites, assessed monoamine oxidase A (MAOA) enzymatic activity, and sequenced the MAOA structural gene in five affected males.
What was found
The condition was characterized by complete and selective loss of MAOA enzymatic activity and altered urinary monoamine metabolism. In each of the five affected males examined, genetic analysis identified a point mutation in exon 8 of the MAOA gene that converted a glutamine codon to a premature stop codon. The abstract reports no quantitative biochemical concentrations or statistical effect estimates.
Why it matters
This study provides foundational evidence that complete, monogenic loss of MAOA function can directly disrupt human monoamine metabolism and correlate with severe behavioral disinhibition and impulsive aggression.
Limits
The study is restricted to five affected males within a single kindred, precluding broad generalization to general aggression. The abstract provides no quantitative biochemical metrics, and the design cannot isolate potential environmental or background genetic modifiers shared within the family.
Cited by
- supports In a studied Dutch family with high rates of male aggression and criminal offenses, affected men inherited a rare mutation in the MAOA gene on the X chromosome.