A first evidence of an asymptomatic germline missense base substitution in the hypoxanthine phosphoribosyltransferase (HPRT) gene in humans.

Abstract

Germline mutations at hypoxanthine phosphoribosyltransferase (HPRT) locus in humans cause HPRT deficiency. Since HPRT gene is on the X chromosome, this genetic disorder is inherited as an X-linked recessive fashion. In the sever form of the disease, designated Lesch-Nyhan syndrome, the affected males develop characteristic neuropsychological symptoms including self-mutilation in addition to hyperuricemia due to urate overproduction. In the milder form, designated partial HPRT deficiency, the patients develop gout, urolithiasis or hyperuricemia but not neurological symptoms. Germline mutations involved in HPRT deficiencies have been extensively analyzed,1 and the accumulated data concerning the molecular abnormalities have been stored in a database.2 Although this database contains numerous germline mutations at the HPRT locus in humans, none of them are asymptomatic mutations; i.e. they are associated with either Lesh-Nyhan syndrome or gout (partial deficiency). Here, we describe, for the first time, a missense base substitution in the germline HPRT gene that caused a reduction in the amount of enzyme per cell but was associated with no recognizable adverse conditions, thus providing the proof that some missense base substitutions in the HPRT gene are asymptomatic.