A SIMPLE, RAPID, AND HIGHLY INFORMATIVE PCR-BASED PROCEDURE FOR PRENATAL-DIAGNOSIS AND CARRIER SCREENING OF PHENYLKETONURIA

The polymorphic information content (PIC) and the degree of heterozygo sity of several polymorphic systems within the phenylalanine hydroxyla se (PAH) gene were determined in 85 European Caucasian and 19 Chinese phenylketonuria (PKU) kindreds. The first system examined, a short tan dem repeat (STR), had a PIC of 80 and 73 per cent in these Caucasian a nd Chinese samples, respectively. The degree of heterozygosity actuall y observed for this system was 81 and 64 per cent in the Caucasian and Chinese PKU families, respectively. Through the addition of a second polymorphism based on a variable number of tandem repeats (VNTR), the PIC was increased to 90 per cent in Caucasians, but only to 75 per cen t in Chinese. The degree of heterozygosity observed for this combinati on was 94 per cent in European PKU families and 67 per cent in Chinese PKU families. The further addition of an Xmnl RFLP increased both the PIC and the level of heterozygosity in Caucasians to 95 per cent, but did not change either of these measures in Chinese. The combined use of these three polymorphisms significantly increases the informativity of prenatal diagnostic and carrier screening procedures in both Cauca sian and Chinese PKU kindreds. Furthermore, since each of these polymo rphisms can be studied by PCR-based methods, these new tests can be pe rformed more quickly and easily than previous Southern-based procedure s.