Preimplantation Genetic Testing for Monogenic Disorders

Abstract

Preimplantation genetic testing (PGT) has evolved into a well-established alternative to invasive prenatal diagnosis, even though genetic testing of single or few cells is quite challenging. PGT-M is in theory available for any monogenic disorder for which the disease-causing locus has been unequivocally identified. In practice, the list of indications for which PGT is allowed may vary substantially from country to country, depending on PGT regulation. Technically, the switch from multiplex PCR to robust generic workflows with whole genome amplification followed by SNP array or NGS represents a major improvement of the last decade: the waiting time for the couples has been substantially reduced since the customized preclinical workup can be omitted and the workload for the laboratories has decreased. Another evolution is that the generic methods now allow for concurrent analysis of PGT-M and PGT-A. As innovative algorithms are being developed and the cost of sequencing continues to decline, the field of PGT moves forward to a sequencing-based, all-in-one solution for PGT-M, PGT-SR, and PGT-A. This will generate a vast amount of complex genetic data entailing new challenges for genetic counseling. In this review, we summarize the state-of-the-art for PGT-M and reflect on its future.

Preimplantation Genetic Testing for Kidney Disease-Related Genes: A Laboratory’s Experience

“…The frequency of chromosome abnormalities in embryos increases with maternal age, but aneuploidy is relatively common across all age groups in embryo samples [14, 15]. Some platforms allow for simultaneous preimplantation genetic testing for aneuploidy (PGT-A) with PGT-M [16], thereby improving implantation and pregnancy rates while decreasing miscarriage rates [17, 18]. In this study, we present a commercial laboratory’s experience with PGT-M for conditions related to primary or secondary kidney disease with concurrent PGT-A.…”

Diagnosis of De Novo Mosaic Balanced Translocation t(1;3)(q42;q25) in a Fetus Conceived Using Pre-implantation Diagnosis Due to Presence in the Father of a Different Balanced Translocation

“…Currently, although there are insu cient data indicating that preimplantation genetic testing (PGT) improves the live birth rate in couples with recurrent miscarriage (RM) carrying a structural chromosome abnormality 3 , PGT is still an established alternative to invasive prenatal diagnosis and as such may avoid adverse pregnancy in couples with structural chromosome abnormalities, and also for a high risk of transmitting genetic disorders [6][7][8] . Although an accurate projection of the anticipated number of unbalanced embryos is not possible at present, con rmation of normal/balanced status results in high pregnancy rates and diagnostic accuracy 9 .…”

Embryo Genetics

“…Six articles cover preimplantation genetic testing at the chromosome and gene levels. A review for genetic disorders covers the evolution of this technology as an established alternative to invasive prenatal diagnosis, as well as future innovations [ 4 ]. The development of new algorithms and the declining costs of sequencing are propelling PGT to a sequencing-based, all-in-one solution for PGT-M, PGT-SR, and PGT-A.…”