Screen for MAOA mutations in target human groups

Brunner et al. [1993: Am J Hum Genet 52: 1032-1039; 1993: Science 262:578-5 80] described males with an MAO-A deficiency state resulting from a prematu re stop codon in the coding region of the MAOA gene. This deficiency state was associated with abnormal levels of amines and amine metabolites in urin e and plasma of affected males, as well as low normal intelligence and appa rent difficulty in impulse control, including inappropriate sexual behavior . In the present study, disruption of the MAOA gene was evaluated in males with mental retardation with and without a history of sexually deviant beha vior, as well as normal controls, healthy males, and patients with other di seases (Parkinson disease, Lesch-Nyhan syndrome). When available, plasma sa mples were evaluated first for levels of 3-methoxy, 4-hydroxyphenolglycol ( MHPG), a metabolite of norepinephrine which serves as the most sensitive in dex of MAO-A activity in humans. Blood DNA from individuals with abnormally low MHPG, and from other individuals for whom metabolite levels were not a vailable, were screened for nucleotide variations in the coding region of t he MAOA gene by single-strand conformational polymorphism (SSCP) analysis a cross all 15 exons and splice junctions, and by sequencing, when indicated by either altered metabolites or SSCP shifts. No evidence for mutations dis rupting the MAOA gene was found in 398 samples from the target populations, including institutionalized mentally retarded males (N = 352) and males pa rticipating in a sexual disorders clinic (N = 46), as well as control group s (N = 75). These studies indicate that MAOA deficiency states are not comm on in humans. Am. J. Med. Genet. (Neuropsychiatr. G;enet.) 88:25-28, 1999. (C) 1999 Wiley-Liss, Inc.