Genetic diagnosis of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) carrier status by restriction analysis and directed mutagenesis

Abstract

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency is transmitted as an X-linked recessive trait. Female carriers are usually asymptomatic. X chromosome inactivation in heterozygous females hematopoietic system may not be random, and few HGPRT negative cells can be found in this tissue (1). The carrier diagnosis is usually performed by determining HGPRT activity in hair roots where HGPRT mosaicism is more evident (2). However, a non-carrier state diagnosis cannot be obtained with absolute certainity. Another limitation of this diagnostic method is the possibility of obtaining nonviable hair roots. Nowadays, genetic analysis must be favoured over biochemical analysis for carrier diagnosis, but not all laboratories have the necessary facilities for this purpose. The knowledge of the genetic mutation in three Spanish families with HGPRT deficiency enabled us to perform the genetic diagnosis of the carrier state in 10 females at risk, in one 9 weeks female fetus, and in a newborn of a carrier female, by using polymorphism restriction analysis and directed mutagenesis (3).