GENETIC DIAGNOSIS OF HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE (HGPRT) - A STUDY OF 12 CASES

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency is t ransmitted as an X-linked recessive trait. Female carriers are asympto matic and the carrier diagnosis is usually performed by determining HG PRT activity in hair roots. This technique does not allow a noncarrier state diagnosis with absolute certainity and has other limitations su ch as obtaining nonviable hair roots, The knowledge of the genetic mut ation in three Spanish families with HGPRT deficiency, enabled us to p erform the genetic diagnosis of the carrier state in 10 female subject s at risk and in one female fetus. The genetic diagnosis has been perf ormed by analyzing the differences between the mutant and the normal a llel with respect to the restriction pattern. When the restriction pat tern showed no differences, this has been created by directed mutagene sis. With this methodology we confirmed that a newborn of a known carr ier female of HGPRT deficiency was healthy, In all cases the diagnosis could be established with great fiability in a mean time of 24 to 48 hours. We report the first genetic diagnosis of the carrier state for the HGPRT deficiency performed in Spain.