Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sex-linked familial neurological disease consisting of cerebral palsy, mental retardation, choreoathetosis, and compulsive aggressive behavior is associated with a loss of an enzyme that participates in purine metabolism, namely, hypoxanthine-guanine phosphoribosyltransferase. The production of excessive uric acid in this disorder implies that the enzyme is involved in the normal regulation of purine biosynthesis. This is the first example of a relation between a specific enzyme defect and abnormal compulsive behavior. It is also the first enzyme defect in purine metabolism demonstrated in a neurological disease.
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PMID:Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. 602 Feb 92

Lesch-Nyhan disease (LND) is a severe X-linked neurological disorder caused by a deficiency of hypoxanthine phosphoribosyltransferase (HPRT). In contrast, HPRT-deficiency in the mouse does not result in the profound phenotypes such as self-injurious behavior observed in humans, and the genetic basis for this phenotypic disparity between HPRT-deficient humans and mice is unknown. To test the hypothesis that HPRT deficiency is modified by the presence/absence of phosphoribosyltransferase domain containing 1 (PRTFDC1), a paralog of HPRT that is a functional gene in humans but an inactivated pseudogene in mice, we created transgenic mice that express human PRTFDC1 in wild-type and HPRT-deficient backgrounds. Male mice expressing PRTFDC1 on either genetic background were viable and fertile. However, the presence of PRTFDC1 in the HPRT-deficient, but not wild-type mice, increased aggression as well as sensitivity to a specific amphetamine-induced stereotypy, both of which are reminiscent of the increased aggressive and self-injurious behavior exhibited by patients with LND. These results demonstrate that PRTFDC1 is a genetic modifier of HPRT-deficiency in the mouse and could therefore have important implications for unraveling the molecular etiology of LND.
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PMID:PRTFDC1 is a genetic modifier of HPRT-deficiency in the mouse. 2181 16