Preimplantation Diagnosis for Single Gene Disorders

Abstract

Preimplantation genetic diagnosis (PGD) allows patients who are carriers or who are affected by genetic diseases to select unaffected embryos for transfer before becoming pregnant. The practice of PGD is evolving with rapid advances in technology and biopsy methods. Testing for a specific gene mutation can be performed in combination with 24-chromosome aneuploidy screening. Several unique applications of PGD are reviewed, including exclusion diagnosis for couples from Huntington disease families, testing for fragile X premutations, and human leukocyte antigen matching for stem cell donor siblings. Although PGD for single gene mutations allows patients to gain information about their embryos and perhaps avoid a difficult decision about whether or not to terminate an ongoing pregnancy, this technique also provides for much ethical debate encompassing the well-being of the prospective couple, embryo, child, and people in the community affected by the diseases being screened.

Genetics in human reproduction

“…In contrast, dominant autosomal disorders usually require testing, even if only one parent has the disease - the case in Huntington's disease. Similarly, women with X-linked recessive disorders should also be counseled about the availability of the test ( Berger & Baker, 2014 ; Janssens et al ., 2014 ; Van Rij et al ., 2012 ; Verlinsky et al ., 1992 ; 2004 ).…”

“…In monogenic diseases, PGT-M is used to detect specific pathogenic variations in the gene sequence associated with certain phenotypes. An example is the association of the ΔF508 mutation and the development of cystic fibrosis (Berger & Baker, 2014). Many genetic variations produce heterogeneous phenotypes in different people due to variable penetrance and expression.…”

“…As only one or a few cells are harvested during biopsy, both techniques require DNA amplification. This has traditionally been done through PCR protocols (Berger & Baker, 2014). More recently, however, some centers have achieved high-quality DNA amplification for monogenic diseases and a screening of 23 pairs of chromosomes using a modified genome-wide amplification protocol (Rechitsky et al, 2013).…”

Molecular analysis of DNA in blastocoele fluid using next-generation sequencing

“…On this basis, the application of PCR-based methods involving mutation detection and linked STRs may be a suboptimal approach for single gene PGD using BF. Nonetheless, a more genome-wide technology such as karyomapping [34][35][36][37] that can analyze a large number of heterogeneous intragenic and intergenic linked SNPs might serve as a more robust approach to single gene PGD using a BF template.…”

Is Day-4 morula biopsy a feasible alternative for preimplantation genetic testing?

“…Preimplantation genetic testing (PGT) allows couples, at risk for transmitting a serious genetic disease, to select unaffected embryos for transfer, and enable the birth of healthy offspring. The main indications for PGT are specific monogenic aberrations and gender related disorders (PGT-M), structural and numerical chromosomal imbalances (PGT-SR), as well as aneuploidy screening (PGT-Aneuploidy PGT-A) [1,2]. Based on single embryonic cell testing, PGT-M has already been applied in a wide range of structural and numerical chromosomal imbalances, monogenic disease, HLA typing, etc., with PGT-polymerase chain reaction (PCR), the method of choice for amplifying the small DNA content achieved from the blastomere biopsy.…”