Ethical considerations in gene selection for reproductive carrier screening

Abstract

Genetic carrier screening for reproductive purposes has existed for half a century. It was originally offered to particular ethnic groups with a higher prevalence of certain severe recessive or X-linked genetic conditions, or (as carrier testing) to those with a family history of a particular genetic condition. Commercial providers are increasingly offering carrier screening on a user-pays basis. Some countries are also trialing or offering public reproductive genetic carrier screening with whole populations, rather than only to those known to have a higher chance of having a child with an inherited genetic condition. Such programs broaden the ethical and practical challenges that arise in clinical carrier testing. In this paper we consider three aspects of selecting genes for population reproductive genetic carrier screening panels that give rise to important ethical considerations: severity, variable penetrance and expressivity, and scalability; we also draw on three exemplar genes to illustrate the ethical issues raised: CFTR, GALT and SERPINA1. We argue that such issues are important to attend to at the point of gene selection for RGCS. These factors warrant a cautious approach to screening panel design, one that takes into account the likely value of the information generated by screening and the feasibility of implementation in large and diverse populations. Given the highly complex and uncertain nature of some genetic variants, careful consideration needs to be given to the balance between delivering potentially burdensome or harmful information, and providing valuable information to inform reproductive decisions.

Views of reproductive genetic carrier screening participants regarding screening for genes associated with non‐syndromic hearing loss

“…The responsible implementation of a publicly funded RGCS program requires careful evaluation to decide which genes should be included, for example, because inclusion can stigmatise people living with the associated genetic condition. This is one reason why screening only for genes associated with severe childhood‐onset conditions is considered the most ethically defensible approach 35–37 . However, debate on what constitutes a severe or serious condition is ongoing, and it is possible that no consensus will be reached.…”

“…This is one reason why screening only for genes associated with severe childhood‐onset conditions is considered the most ethically defensible approach. 35 , 36 , 37 However, debate on what constitutes a severe or serious condition is ongoing, and it is possible that no consensus will be reached.…”

Correspondence on “Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG)” by Gregg et al

“…In addition, variants associated with biochemical features but no clinical phenotype should not be reported. 9 In particular, there is conclusive evidence that the GALT Duarte variant, mentioned in the guideline, is benign. 10 It is acknowledged that there may be some situations in which it would be appropriate to report variants associated with attenuated phenotypes because of potential management implications (eg, mild F8 variants).…”

Views of healthcare professionals on the inclusion of genes associated with non-syndromic hearing loss in reproductive genetic carrier screening

“…There is no consensus definition of disease severity and groups have made different judgements about which conditions are severe enough to include in screening. At a societal level, offering screening for a genetic condition may send a message that using reproductive options to avoid the condition is appropriate [ 10 ]. Programs that screen for a large number of conditions, not all considered severe, have been criticised as they can be perceived to express a discriminatory attitude towards those who live with the condition [ 11 , 12 ].…”