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Science 22 October 1993:
Vol. 262. no. 5133, pp. 578 - 580
DOI: 10.1126/science.8211186
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Articles

Science, Vol 262, Issue 5133, 578-580
Copyright © 1993 by American Association for the Advancement of Science

articles

Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A

HG Brunner, M Nelen, XO Breakefield, HH Ropers, and BA van Oost

Department of Human Genetics, University Hospital Nijmegen, The Netherlands.

Genetic and metabolic studies have been done on a large kindred in which several males are affected by a syndrome of borderline mental retardation and abnormal behavior. The types of behavior that occurred include impulsive aggression, arson, attempted rape, and exhibitionism. Analysis of 24-hour urine samples indicated markedly disturbed monoamine metabolism. This syndrome was associated with a complete and selective deficiency of enzymatic activity of monoamine oxidase A (MAOA). In each of five affected males, a point mutation was identified in the eighth exon of the MAOA structural gene, which changes a glutamine to a termination codon. Thus, isolated complete MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression.


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   Abstract »    Full Text »    PDF »
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   Abstract »    PDF »
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   Abstract »    Full Text »
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   Abstract »    PDF »
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   Abstract »    Full Text »    PDF »
Selective enhancement of emotional, but not motor, learning in monoamine oxidase A-deficient mice.
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »
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(1996)
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   Abstract »    PDF »
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   Abstract »    PDF »
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O Cases, I Seif, J Grimsby, P Gaspar, K Chen, S Pournin, U Muller, M Aguet, C Babinet, J. Shih, et al. (1995)
Science 268, 1763-1766
   Abstract »    PDF »
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JAMA 273, 1715-1716
   Abstract »    PDF »
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J. S Alper (1995)
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   Full Text »
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C Chen, D. Rainnie, R. Greene, and S Tonegawa (1994)
Science 266, 291-294
   Abstract »    PDF »
The genetic basis of complex human behaviors.
R Plomin, M. Owen, and P McGuffin (1994)
Science 264, 1733-1739
   Abstract »    PDF »
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M Simm (1994)
Science 264, 653
   PDF »
Substrate and Inhibitor Specificities for Human Monoamine Oxidase A and B Are Influenced by a Single Amino Acid.
R. M. Geha, I. Rebrin, K. Chen, and J. C. Shih (2001)
J. Biol. Chem. 276, 9877-9882
   Abstract »    Full Text »    PDF »
Pro-apoptotic gene expression mediated by the p38 mitogen-activated protein kinase signal transduction pathway.
G. S. De Zutter and R. J. Davis (2001)
PNAS 98, 6168-6173
   Abstract »    Full Text »    PDF »


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