X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism.
Level 4 - case-series / case-control
Family linkage and biochemical case series
What was done
Linkage analysis using X-chromosome markers was performed in a large Dutch family presenting with X-linked nondysmorphic mild mental retardation and marked behavioral abnormalities. In addition, 24-hour urine analysis was conducted in three affected males to assess monoamine metabolism, and platelet monoamine oxidase type B (MAOB) activity was evaluated.
What was found
The condition mapped to the Xp11-21 interval between markers DXS7 and DXS77, yielding a maximal multipoint LOD score of 3.69 at the MAOA locus (Xp11.23-11.4). 24-hour urine testing in three affected males demonstrated a marked disturbance of monoamine metabolism, while platelet MAOB activity remained normal. Affected males exhibited characteristic impulsive behaviors including violence, arson, attempted rape, exhibitionism, and in one case, attempted suicide; specific numerical rates were not detailed.
Why it matters
This study provides genetic and metabolic linkage connecting isolated monoamine oxidase A deficiency to abnormal monoamine metabolism, mild cognitive impairment, and severe impulsive aggression in humans.
Limits
The study is restricted to a single extended kindred, limiting generalizability. The total number of pedigree members analyzed was not stated in the abstract, and urinary metabolic testing was limited to only three affected individuals. Specific causative DNA sequence variants were not defined in the abstract data.
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.