Preferences of Italian patients for return of secondary findings from clinical genome/exome sequencing

Objective: To evaluate associations between prenatal trio exome sequencing (trio-ES) and psychological outcomes among women with an anomalous pregnancy. Methods: Trio-ES study enrolling patients with major fetal anomaly and normal microarray. Women completed self-reported measures and free response interviews at two time points, pre- (1) and post- (2) sequencing. Pre-sequencing responses were compared to post-sequencing responses; post-sequencing responses were stratified by women who received trio-ES results that may explain fetal findings, secondary findings (medically actionable or carrier couple status), or negative results. Free responses were content analyzed. Results: 115 trios were enrolled. Of those, 41/115 (35.7%) received results from trio-ES, including 36 (31.3%) who received results that may explain the fetal phenotype. These women had greater post-sequencing distress compared to women who received negative results, including generalized distress (p=0.03) and test-related distress (p=0.2); they also had worse psychological adaptation to results (p=0.001). Genomic knowledge did not change from pre- to post-sequencing (p=0.51). Major themes from content analyses included closure, future pregnancy, altruism, anxiety, and gratitude. Conclusions: Women show more distress after receiving trio-ES results compared to those who do not.

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Delivering genome sequencing in clinical practice: an interview study with healthcare professionals involved in the 100 000 Genomes Project

BMJ Open ◽

10.1136/bmjopen-2019-029699 ◽

2019 ◽

Vol 9 (11) ◽

pp. e029699 ◽

Cited By ~ 3

Author(s):

Saskia C Sanderson ◽

Melissa Hill ◽

Christine Patch ◽

Beverly Searle ◽

Celine Lewis ◽

...

Keyword(s):

Exome Sequencing ◽

Genome Sequencing ◽

Rare Diseases ◽

Healthcare Professionals ◽

Diagnostic Yield ◽

Clinical Care ◽

Vital Role ◽

Interview Study ◽

Secondary Findings ◽

Policy And Practice

ObjectivesGenome sequencing is poised to be incorporated into clinical care for diagnoses of rare diseases and some cancers in many parts of the world. Healthcare professionals are key stakeholders in the clinical delivery of genome sequencing-based services. Our aim was to explore views of healthcare professionals with experience of offering genome sequencing via the 100 000 Genomes Project.DesignInterview study using thematic analysis.SettingFour National Health Service hospitals in London.ParticipantsTwenty-three healthcare professionals (five genetic clinicians and eight non-genetic clinicians (all consultants), and 10 ‘consenters’ from a range of backgrounds) involved in identifying or consenting patients for the 100 000 Genomes Project.ResultsMost participants expressed positive attitudes towards genome sequencing in terms of improved ability to diagnose rare diseases, but many also expressed concerns, with some believing its superiority over exome sequencing had not yet been demonstrated, or worrying that non-genetic clinicians are inadequately prepared to discuss genome sequencing results with patients. Several emphasised additional evidence about utility of genome sequencing in terms of both main and secondary findings is needed. Most felt non-genetic clinicians could support patients during consent, as long as they have appropriate training and support from genetic teams. Many stated genetics experts will play a vital role in training and supporting non-genetic clinicians in variant interpretation and results delivery, particularly for more complex cases.ConclusionsHealthcare professionals responsible for delivering clinical genome sequencing have largely positive views about the potential for genome sequencing to improve diagnostic yield, but also significant concerns about practical aspects of offering these tests. Non-genetic clinicians delivering genome sequencing require guidance and support. Additional empirical evidence is needed to inform policy and practice, including how genome compares to exome sequencing; utility of secondary findings; training, in particular of non-genetic health professionals; and mechanisms whereby genetics teams can offer appropriate support to their non-genetics colleagues.

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