amanitins and Lesch-Nyhan-Syndrome

The hypoxanthine phosphoribosyl transferase (HPRT) and adenine phosphoribosyl transferase (APRT) activities in individual non-fertilized human eggs and in human pre-embryos (4-cell to blastocyst stage) have been analysed. A wide spread of activities was observed, the mean values of which decline with time post-ovulation for both eggs and advancing pre-embryonic stages. The variation in activities was less in groups of eggs or pre-embryos recovered from a single ovulatory cycle. The activity of HPRT, but not of APRT, was readily detectable in single 4-cell and 8-cell blastomeres. When pre-embryos at various preimplantation stages were exposed to alpha-amanitin, to block transcription of mRNA from the pre-embryonic genome, no clear effect on HPRT activity was observed. It is concluded that the HPRT and APRT activities measured in the pre-embryos studied here are likely to be maternally inherited, and that use of a direct assay for HPRT activity for the pre-implantation diagnosis of Lesch-Nyhan disease would be premature.

Topics: Adenine Phosphoribosyltransferase; Amanitins; Embryonic Development; Female; Humans; Hypoxanthine Phosphoribosyltransferase; In Vitro Techniques; Lesch-Nyhan Syndrome; Oocytes; Pentosyltransferases; Pregnancy; Prenatal Diagnosis; Transcription, Genetic; Zygote