Carrier Screening: Past, Present, and Future

Bajaj, Komal; Gross, Susan J.

doi:10.3390/jcm3031033

Cited by 26 publications

(24 citation statements)

References 26 publications

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“…They gave consent for WES, including for their own DNA, in a research setting. The genetic cause of the child's disease was established in four couples (1,5,6, and 7) ( Table 1); the affected child was homozygous for the causative mutation(s) and the parents were identified as heterozygous carriers. Couples 1, 3, 5, 6, and 7 were of Moroccan origin, couples 4 and 8 were from Turkey, and couple 2 was from Iraq (Supplementary Table S1 online).…”

Section: Subjectsmentioning

confidence: 99%

“…5 The concept of PCS has been applied for decades in some of these populations. 6 Typically, one or a few diseases with a relatively high incidence in a population, or subpopulation, are tested in a targeted manner. 5 However, with the introduction of next-generation sequencing techniques, simultaneous testing of much larger gene numbers has become possible and cost-effective.…”

Section: Introductionmentioning

confidence: 99%

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A comprehensive strategy for exome-based preconception carrier screening

Sallevelt

Koning

Szklarczyk

et al. 2017

Genetics in Medicine

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Purpose: Whole-exome sequencing (WES) provides the possibility of genome-wide preconception carrier screening (PCS). Here, we propose a filter strategy to rapidly identify the majority of relevant pathogenic mutations. Methods:Our strategy was developed using WES data from eight consanguineous and five fictive nonconsanguineous couples and was subsequently applied to 20 other fictive nonconsanguineous couples. Presumably pathogenic variants based on frequency and database annotations or generic characteristics and mutation type were selected in genes shared by the couple and in the female's X-chromosome. Unclassified variants were not included. Results:This yielded an average of 29 (19-51) variants in genes shared by the consanguineous couples and 15 (6-30) shared by the nonconsanguineous couples. For X-linked variants, the numbers per female were 3 (1-5) and 1 (0-3), respectively. Remaining variants were verified manually. The majority were able to be quickly discarded, effectively leaving true pathogenic variants. Conclusion:We conclude that WES is applicable for PCS, both for consanguineous and nonconsanguineous couples, with the remaining number of variants being manageable in a clinical setting. The addition of gene panels for filtering was not favorable because it resulted in missing pathogenic variants. It is important to develop and continuously curate databases with pathogenic mutations to further increase the sensitivity of WES-based PCS.

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Section: Subjectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A comprehensive strategy for exome-based preconception carrier screening

Sallevelt

Koning

Szklarczyk

et al. 2017

Genetics in Medicine

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“…Traditionally, PCS has been limited to a small number of specific tests and generally offered to certain (often ethnic) high-risk populations (5). However, advancements in genomics have opened new possibilities for carrier screening in whole populations without a prior risk or family history; in the US for example, the American College of Medical Genetics recommends all couples regardless of ancestry or geographic origin to be offered screening for SMA (6), and the American College of Obstetricians & Gynecologists recommends all women of reproductive age (regardless of ancestry or geographic origin) to be offered screening for CF (7).…”

Section: Introductionmentioning

confidence: 99%

“…This allows screening for the carrier status of a large number of inherited conditions at one go (8–10). The new technology has also opened up for commercial companies to offer a wide array of genetic screening tests and services, either directly to the consumer, or via referrals from private health care providers (5). …”

Section: Introductionmentioning

confidence: 99%

Swedish parents’ interest in preconception genetic carrier screening

Ragnar

Tydén

Kihlbom

et al. 2016

Upsala Journal of Medical Sciences

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IntroductionGenetic technologies advance rapidly. It is possible to undergo genetic carrier screening before pregnancy to examine genetic risks to future offspring. We aimed to investigate parents’ interest and motives towards preconception genetic carrier screening (PCS) as well as factors associated with interest in PCS.Material and methodsOur study sample consists of 777 parent couples within the longitudinal Swedish Pregnancy Planning study. Women responded to questionnaires at three occasions: in early pregnancy, late pregnancy, and one year after childbirth. Male partners responded to one questionnaire one year after childbirth.ResultsOne-third of the parents were positive (30% versus 34% of women and men, respectively), less than a third were negative (26% versus 28%), and 45% versus 38% were uncertain about whether to consider PCS before a future pregnancy. No differences in PCS interest were found between women and men (P = 0.091), but a higher proportion of women were concerned about negative consequences (53% versus 46%, P < 0.003) and were ‘opposed to such a way of child selection’ (31.8% versus 25.2%, P = 0.002). Factors associated with PCS interest were experiences of prenatal diagnostics and positive attitudes towards finding out or choosing sex of one’s child (women), and prenatal diagnostics, self-rated poor health, and pregnancy planning (men).ConclusionBoth women and men had relatively high uncertainty towards PCS, but women were more concerned about negative consequences. The future extent of the clinical utility of PCS is currently unknown, but parents’ interests and doubts are important aspects to consider.

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“…Today, in the US, carrier screening for the entire reproductive population is only recommended for cystic fibrosis and there are inconsistent and sometimes contradictory policies targeting specific populations for other disorders. 12 For example, consider the situation for carrier screening for the hemoglobinopathies in the US. According to the California Newborn Screening Program (CNSP), there are approximately 29.5 per 100,000 births (1/3,390) affected by sickle cell, an alpha or beta thalassemia disorder.…”

Section: For (Peter Benn)mentioning

confidence: 99%

Current controversies in prenatal diagnosis 4: pre-conception expanded carrier screening should replace all current prenatal screening for specific single gene disorders

2015

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What's already known about this topic?In the United States there is increasing availability of pan‐ethnic carrier screening covering mutations in a large number of genes (“expanded screening”).A large‐scale study on the use of expanded carrier screening has been published by a commercial laboratory offering this test.The American College of Medical Genetics and Genomics has issued a position statement on prenatal/preconception expanded carrier screening. What does the study add?This report summarizes an oral debate presented at the 18th International Conference on Prenatal Diagnosis and Therapy in Brisbane, Australia on 23 July 2014.The benefits, limitations, and challenges of preconception expanded carrier screening are discussed.

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Carrier Screening: Past, Present, and Future

Cited by 26 publications

References 26 publications

A comprehensive strategy for exome-based preconception carrier screening

A comprehensive strategy for exome-based preconception carrier screening

Swedish parents’ interest in preconception genetic carrier screening

Current controversies in prenatal diagnosis 4: pre-conception expanded carrier screening should replace all current prenatal screening for specific single gene disorders

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