Preimplantation genetic testing for more than one genetic condition: clinical and ethical considerations and dilemmas

Abstract

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Novel Compound Heterozygous Mutations in CRTAP Cause Rare Autosomal Recessive Osteogenesis Imperfecta

“…The expanded carrier screening is of importance to identify such variants in couples before pregnancy. Once the couples are found to be at risk for transmitting certain types of diseases, in vitro fertilization and preimplantation genetic testing (PGT) for monogenic disorders may be considered to stop transmitting deleterious variants into the next generation ( Daar et al, 2018 ; Fu et al, 2019 ; van der Schoot et al, 2019 ).…”

“…To analyze the regional DNA copy changes from each WES sample, the CNVkit (Talevich et al, 2016) that uses both the targeted reads and the non-specifically captured off-target reads to infer copy number evenly across the genome was applied, and this was generated by the BWA-MEM algorithm. Briefly, the target and off-target coverages of each sample were calculated based on the read counts per bin using the BAM file as input.…”

“…We suspect that the mother may have a deletion within this region. To analyze CNV, we applied the CNVkit, a tool developed specifically to call CNV using data from WES or targeted-seq (Talevich et al, 2016), to search for the explanation for the missing maternal allele. Results from the CNVkit clearly showed that the mother carried a ∼1.81 Mb deletion at chr3p22.3 (hg19, chr3:g.32398837_34210906del), and she passed this deletion to the proband, while the father did not have any CNV at this region ( Figure 3A).…”

Preimplantation genetic testing: comparative analysis of jurisprudential regulations

“…Indeed, the level of difficulty to overcome the status of infertile couple, and then the concrete chance to achieve a pregnancy, can influence the opinion regarding the gravity of a genetic condition. In recent decades, indications for PGT increased, being included also diseases characterized by incomplete penetrance, adult-onset, treatable or amenable to screening (ovarian or breast cancer, hypertrophic cardiomyopathy) conditions (43). Sex selection can be morally acceptable if the goal is to avoid genetic diseases inherited by sex chromosomes, while is generally considered ethically unacceptable if used to choose the unborn gender (44).…”

Professionals’ Views on Offering Pre-Natal Testing for Adult Onset Cancer Susceptibility. Reconciling Personal and Professional Ethical Conflicts, Coping Strategies and Need for Policy Transparency

“…Preimplantation Genetic Testing (PGT) 2 is an alternative that avoids terminating a pregnancy for patients with some genetic conditions [9][10][11]. The regulations around PGT are variable across Europe [12] and controversially PGT is not regulated in the USA [13]. In the UK PGT is regulated by the Human Fertility and Embryology Association (HFEA) and it is offered through the NHS to prospective parents who meet strict personal health and social criteria (NHS England Clinical Reference Group for Medical Genetics 2014) [14].…”