POLYMORPHISMS IN THE ALANINE-GLYOXYLATE AMINOTRANSFERASE GENE AND THEIR APPLICATION TO THE PRENATAL-DIAGNOSIS OF PRIMARY HYPEROXALURIA TYPE-1

Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the he patic alanine:glyoxylate aminotransferase enzyme encoded by the AGXT g ene on chromosome 2. Prenatal diagnosis of PH1 either by measurement o f hepatic enzyme activity or DNA analysis provides a valuable contribu tion to the management of pregnancies at risk for the severe infantile form of this disease. DNA analysis is preferred because it can be per formed earlier in pregnancy and eliminates difficulties encountered in measurement of tissue enzyme activity, particularly those related to sample instability. We have assessed the clinical value of two polymor phisms located in introns 1 and 4 of the AGXT gene as linkage markers for the prenatal diagnosis of PH1 in 12 families. Eight of the twelve families were informative when either one or a combination of the two polymorphisms was used and prenatal diagnosis has been performed in tw o of these. The remaining four families were only partially informativ e. Five additional linkage markers on chromosome 2 have been identifie d which are co-inherited with the AGXT gene. Assays to detect these ma rkers are currently under development.