Next generation sequencing is a highly reliable method to analyze exon 7 deletion of survival motor neuron 1 (SMN1) gene

Spinal muscular atrophy (SMA) is one of the most common and severe genetic diseases. SMA carrier screening is an effective way to identify couples at risk of having affected children. Next-generation sequencing (NGS)-based expanded carrier screening could detect SMN1 gene copy number without extra experiment and with high cost performance. However, its performance has not been fully evaluated. Here we conducted a systematic comparative study to evaluate the performance of three common methods. 478 samples were analyzed with multiplex ligation probe amplification (MLPA), real-time quantitative polymerase chain reaction (qPCR) and NGS, simultaneously. Taking MLPA-based results as the reference, for 0 copy, 1 copy and ≥ 2 copy SMN1 analysis with NGS, the sensitivity, specificity and precision were all 100%. Using qPCR method, the sensitivity was 100%, 97.52% and 94.30%, respectively; 98.63%, 95.48% and 100% for specificity; and 72.72%, 88.72% and 100% for precision. NGS repeatability was higher than that of qPCR. Moreover, among three methods, NGS had the lowest retest rate. Thus, NGS is a relatively more reliable method for SMN1 gene copy number detection. In expanded carrier screening, compared with the combination of multiple methods, NGS method could reduce the test cost and simplify the screening process.

Population-based Carrier Screening for Spinal Muscular Atrophy in Saudi Arabia

Spinal Muscular Dystrophy (SMA) is one of the leading causes of death in children from heritable diseases. It is reported that the incidence of SMA is higher in the Saudi population. 4198 healthy volunteers between 18 to 25 years old were included in this study of which (54.7% males vs 45.3% females). Whole blood was spotted from finger pricks onto IsoCode StixTM and genomic DNA was isolated using one triangle from the machine. Carrier frequency and population-level data were used to estimate the prevalence of SMA in the population utilizing the life table method. Results showed the presence of one copy of the SMN1 gene in 108 samples, two copies in 4090 samples, and a carrier frequency of 2.6%. Carrier figurine was twofold in females and 27% of participants were children of first-cousin marriages. The birth incidence of SMA was estimated to be 32 per 100,000 birth and the total number of people living with SMA in KSA to be 2,265 of which 188 are type I, 1,213 are type II, and 864 are type III. The SMA carrier rate of 2.6 % in Saudi subjects is slightly higher than the reported global frequency with links to the consanguineous marriages.

Qualitative study of GPs’ views and experiences of population-based preconception expanded carrier screening in the Netherlands: bioethical perspectives

ObjectiveBetween 2016 and 2017, a population-based preconception expanded carrier screening (PECS) test was developed in the Netherlands during a pilot study. It was subsequently made possible in mid-2018 for couples to ask to have such a PECS test from specially trained general practitioners (GPs). Research has described GPs as crucial in offering PECS tests, but little is known about the GPs’ views on PECS and their experiences of providing this test. This article presents a thematic analysis of the PECS practice from the perspective of GPs and a bioethical discussion of the empirical results.DesignEmpirical bioethics. A thematic analysis of qualitative semi-structured interviews was conducted, and is combined with an ethical/philosophical discussion.SettingThe Netherlands.Participants7 Dutch GPs in the Netherlands, interviewed in 2019–2020.ResultsTwo themes were identified in the thematic analysis: ‘Choice and its complexity’ and ‘PECS as prompting existential concerns’. The empirical bioethics discussion showed that the first theme highlights that several areas coshape the complexity of choice on PECS, and the need for shared relational autonomous decision-making on these areas within the couple. The second theme highlights that it is not possible to analyse the existential issues raised by PECS solely on the level of the couple or family. A societal level must be included, since these levels affect each other. We refer to this as ‘entangled existential genetics’.ConclusionThe empirical bioethical analysis leads us to present two practical implications. These are: (1) training of GPs who are to offer PECS should cover shared relational autonomous decision-making within the couple and (2) more attention should be given to existential issues evoked by genetic considerations, also during the education of GPs and in bioethical discussions around PECS.

Decision-making for prenatal genetic screening: how will pregnant women navigate a growing number of aneuploidy and carrier screening options?

Background Prenatal genetic screens, including carrier screening (CS) and aneuploidy screening (AS), comprise an important component of reproductive healthcare delivery. Clinical practice guidelines emphasize the importance of informed decision-making and patient’s preferences regarding the use of these screens. Yet, it is unclear how to achieve this ideal as prenatal genetic screening options rapidly become more complex and increasingly available to patients. With increased complexity and availability of reproductive testing options, decision-support strategies are critical to prepare patients to consider AS and/or CS. Methods A self-administered survey evaluated knowledge and decision-making preferences for expanded carrier (CS) and aneuploidy (AS) prenatal screening. The survey was administered to participants before their first prenatal visit to assess baseline decision-making needs and preference at the initiation of prenatal care. Analysis was approached as a descriptive process. Results Participants had similar familiarity with the concepts associated with AS compared to CS; mean knowledge scores for CS was 0.59 [possible range 0.00 to 1.00] and 0.55 for AS. Participants reported preferences to learn about a range of conditions, including those with severe or mild impact, childhood-onset, and adult-onset. Decision-making preference with respect to learning about the associated disease phenotypes for the contained on AS and CS panel shifted with the complexity of the panel, with a greater preference to learn about conditions post-test compared pre-test education as panels increased from 5 to 100 conditions. Conclusion Patients’ baseline knowledge of prenatal genetic screens coupled with evolving decision-making preferences presents challenges for the delivery of prenatal genetic screens. This calls for the development and implementation of innovative approaches to support pregnant patients’ decision-making commensurate with advances in prenatal genomics.