DETECTION OF A NOVEL SPLICE VARIANT OF THE HYPOXANTHINE-GUANINE PHOSPHORIBOSYL TRANSFERASE GENE IN HUMAN OOCYTES AND PREIMPLANTATION EMBRYOS - IMPLICATIONS FOR A RT-PCR-BASED PREIMPLANTATION DIAGNOSIS OF LESCH-NYHAN-SYNDROME

We have detected a novel splice variant of the hypoxanthine-guanine ph osphoribosyl transferase (HPRT) gene in two human oocytes and four pre implantation embryos from the 4-cell to the 8-cell stage of developmen t. The novel HPRT transcript lacks exons 4, 5 and 6 of the normal HPRT gene. The same parental origin for the two oocytes and two of the pre implantation embryos, in which the alternatively spliced transcript wa s detected, might suggest that the alternative splicing is influenced by genetic background, Mutations in the HPRT gene which cause alternat ive mRNA splicing are implicated in Lesch-Nyhan syndrome. However, the relatively high frequency of detection of this novel HPRT transcript described here (6/109 oocytes and preimplantation embryos) suggests th at it is not involved in Lesch-Nyhan syndrome, It is probable that the alternative HPRT transcript is derived from the aberrant splicing of a small percentage of the total mRNA produced from normal HPRT alleles . The presence of this alternative transcript in human preimplantation embryos may complicate an reverse transcription-polymerase chain reac tion-based preimplantation diagnosis of Lesch-Nyhan syndrome.