International perspectives on the implementation of reproductive carrier screening

Delatycki, Martin B.; Alkuraya, Fowzan S.; Archibald, Alison D; Castellani, Carlo; Cornel, Martina C.; Grody, Wayne W.; Henneman, Lidewij; Ioannides, Adonis S.; Kirk, Edwin P.; Laing, Nigel G.; Lucassen, Anneke; Massie, John; Schuurmans, Juliëtte; Thong, Meow‐Keong; Langen, Irene M. van; Zlotogora, Joël

doi:10.1002/pd.5611

Cited by 74 publications

(69 citation statements)

References 64 publications

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“…Expanded preconception carrier screening for CF and other recessive disorders is also under consideration in countries according to an overall positive attitude of the general population [ 70 , 71 ]. Preconception CF carrier screening has already been implemented in the US, Israël and Northeast Italy [ 72 ]. In most countries however, for practical reasons variant panels used for diagnostic purposes are also used for carrier testing.…”

Section: The Challenges Of Genetic Counseling—when Genetic Counselmentioning

confidence: 99%

Molecular Diagnosis and Genetic Counseling of Cystic Fibrosis and Related Disorders: New Challenges

Bienvenu

Lopez

Girodon

2020

Genes

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Identification of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and its numerous variants opened the way to fantastic breakthroughs in diagnosis, research and treatment of cystic fibrosis (CF). The current and future challenges of molecular diagnosis of CF and CFTR-related disorders and of genetic counseling are here reviewed. Technological advances have enabled to make a diagnosis of CF with a sensitivity of 99% by using next generation sequencing in a single step. The detection of heretofore unidentified variants and ethnic-specific variants remains challenging, especially for newborn screening (NBS), CF carrier testing and genotype-guided therapy. Among the criteria for assessing the impact of variants, population genetics data are insufficiently taken into account and the penetrance of CF associated with CFTR variants remains poorly known. The huge diversity of diagnostic and genetic counseling indications for CFTR studies makes assessment of variant disease-liability critical. This is especially discussed in the perspective of wide genome analyses for NBS and CF carrier screening in the general population, as future challenges.

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Section: The Challenges Of Genetic Counseling—when Genetic Counselmentioning

confidence: 99%

Molecular Diagnosis and Genetic Counseling of Cystic Fibrosis and Related Disorders: New Challenges

Bienvenu

Lopez

Girodon

2020

Genes

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“…Expanded preconception carrier screening for recessive disorders is also under consideration in countries following an overall positive attitude of the general population [69], depending on ethnical and geographical origin, degree of consanguinity, and type of disorders. Preconception CF carrier screening has already been implemented in the US, Israël, and Northeast Italy [70]. Such a health public policy aims to detect most at-risk couples and this ineluctably impacts on the timing for a CF diagnosis and on the prevalence of CF births [71], which would then raise the question of the relevance of NBS.…”

Section: Discussionmentioning

confidence: 99%

The Role of Extended CFTR Gene Sequencing in Newborn Screening for Cystic Fibrosis

Bergougnoux

Lopez

Girodon

2020

IJNS

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There has been considerable progress in the implementation of newborn screening (NBS) programs for cystic fibrosis (CF), with DNA analysis being part of an increasing number of strategies. Thanks to advances in genomic sequencing technologies, CFTR-extended genetic analysis (EGA) by sequencing its coding regions has become affordable and has already been included as part of a limited number of core NBS programs, to the benefit of admixed populations. Based on results analysis of existing programs, the values and challenges of EGA are reviewed in the perspective of its implementation on a larger scale. Sensitivity would be increased at best by using EGA as a second tier, but this could be at the expense of positive predictive value, which improves, however, if EGA is applied after testing a variant panel. The increased detection of babies with an inconclusive diagnosis has proved to be a major drawback in programs using EGA. The lack of knowledge on pathogenicity and penetrance associated with numerous variants hinders the introduction of EGA as a second tier, but EGA with filtering for all known CF variants with full penetrance could be a solution. The issue of incomplete knowledge is a real challenge in terms of the implemention of NBS extended to many genetic diseases.

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“…However, the reverse argument was made recently: If a treatment becomes available that increases the societal and especially economic impact of a disorder, this may become a burden for society, thus making preconception carrier screening even more urgent (Sinha et al 2020). This resembles the arguments on carrier screening for ß-thalassemia in Cyprus in the early1970s (Delatycki et al 2020).…”

Section: How Innovations Make Debates Convergementioning

confidence: 99%

Neonatal and carrier screening for rare diseases: how innovation challenges screening criteria worldwide

et al. 2020

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Screening for rare diseases first began more than 50 years ago with neonatal bloodspot screening (NBS) for phenylketonuria, and carrier screening for Tay-Sachs disease, sickle cell anaemia and β-thalassaemia. NBS’s primary aim is health gain for children, while carrier screening enables autonomous reproductive choice. While screening can be beneficial, it also has the potential to cause harm and thus decisions are needed on whether a specific screening is worthwhile. These decisions are usually based on screening principles and criteria. Technological developments, both treatment driven and test driven, have led to expansions in neonatal screening and carrier screening. This article demonstrates how the dynamics and expansions in NBS and carrier screening have challenged four well-known screening criteria (treatment, test, target population and programme evaluation), and the decision-making based on them. We show that shifting perspectives on screening criteria for NBS as well as carrier screening lead to converging debates in these separate fields. For example, the child is traditionally considered to be the beneficiary in NBS, but the family and society can also benefit. Vice versa, carrier screening may be driven by disease prevention, rather than reproductive autonomy, raising cross-disciplinary questions regarding potential beneficiaries and which diseases to include. In addition, the stakeholders from these separate fields vary: Globally NBS is often governed as a public health programme while carrier screening is usually available via medical professionals. The article concludes with a call for an exchange of vision and knowledge among all stakeholders of both fields to attune the dynamics of screening.

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International perspectives on the implementation of reproductive carrier screening

Cited by 74 publications

References 64 publications

Molecular Diagnosis and Genetic Counseling of Cystic Fibrosis and Related Disorders: New Challenges

Molecular Diagnosis and Genetic Counseling of Cystic Fibrosis and Related Disorders: New Challenges

The Role of Extended CFTR Gene Sequencing in Newborn Screening for Cystic Fibrosis

Neonatal and carrier screening for rare diseases: how innovation challenges screening criteria worldwide

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