Candidate genes MAOA

Question 1

MAOA gene?

Answer 1

• A mitochondrial enzyme that breaks down NT including DA and serotoning
• Gene located on X chromosome.

Question 2

Genetic and metabolic studies on a large kinderen in which several males are affected by a syndrome of borderline mental retardation, and abnormal behaviour (including impulsive aggression, arson, attempted rape, exhibitionism)

• Brunner’s syndrome” isolated complete MAOA deficiency in this family is associated with a recognizable behavioural phenotype that includes disturbed regulation of impulsive aggression.
• Analysis of urine samples indicated markedly disturbed monamine metabolism.
• This syndrome was associated with a complete and selective deficiency of MAOA enzymatic activity.
• In each of 5 affected males, a point mutation was identified in the 8th exon of the MAOA structural gene: changed a glutamine to a termination codon, i.e. a nonsense mutation)

Answer 2

Brunner 1993

Question 3

Performed high-throughput target sequencing of 220 genes including MAOA in pateienst with undiagnosed intellectual disability.

• Identified a missense mutation in MAOA in a boy with autism spectrm disorders, attention deficit and autoaggressive behaviour. Two maternal uncles carrey the mutation and have severe ID, with a history of maltreatment in early childohood.
• Novel missense mutation decreases MAOA activity, causes abnormal levels of urinary monoamines.
• ‘The identification of this new point mutation confurms… the monogenic implication of the MAOA gene in ID of various degrees, autism and behavioural disturbances;.

Answer 3

Piton et al 2014