40. SIMULTANEOUS PREIMPLANTATION GENETIC TESTING (PGT) FOR 5 DIFFERENT GENETIC CONDITIONS

Abstract

Introduction It is a common practice to perform PGT-M for one or two disorders at the same test, but it is the first PGT performed simultaneously for 5 different conditions, which is presented below. Material and Methods Consanguineous couple presented for PGT-M to avoid the risk of producing another affected child homozygous for four different autosomal recessive conditions identified in their previous offspring, including: (1) early infantile epileptic encephalopathy 5 (EIEE5), caused by SPTAN1 mutation; (2) xeroderma pigmentosum-complementation group C (XPG), caused by ERCC5 mutation; (3) congenital merosin–deficient muscular dystrophy 1A (MDC1A), caused by LAMA2 mutation; and (4) phenylketonuria (PKU) caused by PAH mutation. As parents requested also aneuploiidy testing, PGT design was to combine PGT-A and PGT-M, involving mutation and linked marker testing by multiplex nested PCR, to avoid the undetected ADO of each of the genes tested. Results Overall, 12 of 16 embryos reaching the blatocyst stage were tested together with NGS for PGT-A, of which 10 were affected, including 6 affected by one mutation, and four by two mutations. Only 2 embryos were unaffected carriers of all 4 gene mutations, of which one was with trisomy 13, so only a single embryos euploid and carrier of all 4 gene mutations was transferred, resulting, resulting in birth of a healthy unaffected baby. Although a cumulative risk of couple for producing an offspring affected by all the four conditions is only 0.4%, the couple still has been very unfortunate to produce such a child in their natural cycle. Although the chance for detecting unaffected embryo was also not high enough (31.6%), especially by added 50% risk for aneuploidy (15.8%), still one of 12 embryos tested was both euploid and normal carrier of all the mutations, resulting in a healthy, unaffected child. Conclusions This is the world's first PGT for 5 different genetic conditions (EIEE5, XPG, MDC1A, PKU and aneuploidy) in a single test, resulting in a transfer of euploid embryo free of all the conditions tested, demonstrating feasibility and accuracy of simultaneous combined PGT for multiple genetic conditions.