20 ans après: a second mutation in MAOA identified by targeted high-throughput sequencing in a family with altered behavior and cognition.
Level 4 - case-series / case-control
Family case study and pedigree genetic analysis.
PubMed 24169519 · doi:10.1038/ejhg.2013.243
What was done
Targeted high-throughput sequencing of 220 genes, including MAOA, was performed in patients with undiagnosed intellectual disability (ID). Familial segregation, MAOA enzymatic activity, and urinary monoamines were analyzed in identified mutation carriers.
What was found
A novel missense mutation in MAOA (c.797_798delinsTT, p.C266F) was identified in a boy with autism spectrum disorder, attention deficit, and autoaggressive behavior, as well as two maternal uncles with severe ID. The mutation decreased MAOA enzymatic activity and altered urinary monoamine levels. The abstract does not provide specific numerical values.
Why it matters
This represents the second family described with a monogenic MAOA mutation linked to intellectual disability and behavioral alterations since the 1993 Brunner syndrome report, highlighting phenotypic variability across affected males.
Limits
The study is restricted to a single family with three affected individuals. The total number of screened patients, precise biochemical measurements, and controlled verification of proposed gene-environment interactions are absent from the abstract.