Published online Oct 16, 2021. doi: 10.12998/wjcc.v9.i29.8797
Peer-review started: December 16, 2020
First decision: July 16, 2021
Revised: July 28, 2020
Accepted: September 7, 2021
Article in press: September 7, 2021
Published online: October 16, 2021
Processing time: 296 Days and 7.3 Hours
Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities' current methodology for screening, which focuses on the detecting multiple genetic disorders at once. Here, we report the successful application of a low-cost and fast preimplantation genetic testing for monogenic/single gene defects (PGT-M) approach for detecting propionic acidemia (PA) in embryos obtained from a confirmed heterozygous propionyl-CoA carboxylase alpha subunit (PCCA) couple.
A fertile 32-years old Mexican couple with denied consanguinity sought antenatal genetic counseling. They were suspected obligate PA carriers due to a previous deceased PA male newborn with an unknown PCCA/propionyl-CoA carboxylase beta subunit (PCCB) genotype. Next-Generation Sequencing revealed a heterozygous genotype for a pathogenic PCCA variant (c.2041-1G>T, ClinVar:RCV
We show that using PGT-M with Whole Genome Amplification templates, coupled with IVF, can reduce the transmission of a pathogenic variant of the PCCA gene.
Core Tip: Propionic acidemia is an uncommon monogenetic disorder resulting in inherited severe complications and death. A heterozygous genotype for a pathogenic variant of the propionyl-Coenzyme A carboxylase alpha subunit gene (PCCA) was located in a fertile Mexican couple. Here we show that a couple can reduce the transmission of a pathogenic variant of a gene using in vitro fertilization, genetic counseling, and sequencing of a whole genome amplification template. Furthermore, after embryo transfer, we report the delivery of a healthy male newborn without propionic acidemia.