Towards a European consensus for reporting incidental findings during clinical NGS testing.

In 2013, the American College of Medical Genetics (ACMG) examined the issue of incidental findings in whole exome and whole genome sequencing, and introduced recommendations to search for, evaluate and report medically actionable variants in a set of 56 genes. At a debate held during the 2014 European Society for Human Genetics Conference (ESHG) in Milan, Italy, the first author of that paper presented this view in a debate session that did not end with a conclusive vote from the mainly European audience for or against reporting back actionable incidental findings. In this meeting report, we elaborate on the discussions held during a special meeting hosted at the ESHG in 2013 from posing the question 'How to reach a (European) consensus on reporting incidental findings and unclassified variants in diagnostic next generation sequencing'.

Focus group discussions on secondary variants and next-generation sequencing technologies.

The clinical application of new genetic technologies will be and already is of great benefit to children with unexplained developmental disabilities or congenital anomalies. In most cases, it will be their parents who, together with medical professionals, make decisions about what should be disclosed and how the information will be used. We conducted eight exploratory focus group discussions with stakeholders to provide a broad sketch of concerns and ideas around the communication of results from next-generation sequencing technologies involving children.

Ethical signposts for clinical geneticists in secondary variant and incidental finding disclosure discussions.

While ethical and empirical interest in so-called secondary variants and incidental findings in clinical genetics contexts is growing, critical reflection on the ethical foundations of the various recommendations proposed is thus far largely lacking. We examine and critique the ethical justifications of the three most prominent disclosure positions: briefly, the clinical geneticist decides, a joint decision, and the patient decides. Subsequently, instead of immediately developing a new disclosure option, we explore relevant foundational ethical values and norms, drawing on the normative and empirical ethical literature.

A prospective study of the clinical utility of prenatal chromosomal microarray analysis in fetuses with ultrasound abnormalities and an exploration of a framework for reporting unclassified variants and risk factors.

Purpose: To evaluate the clinical utility of chromosomal microarrays for prenatal diagnosis by a prospective study of fetuses with abnormalities detected on ultrasound.

Methods: Patients referred for prenatal diagnosis due to ultrasound anomalies underwent analysis by array comparative genomic hybridization as the first-tier diagnostic test.

Results: A total of 383 prenatal samples underwent analysis by array comparative genomic hybridization.

Disclosing incidental findings in genetics contexts: a review of the empirical ethical research.

The disclosure of incidental findings, also called unsolicited findings, unexpected results, and secondary variants, is increasingly recognised as an issue in clinical and research genetics contexts. The rise of next generation sequencing methods has only intensified the issue, increasing the likelihood of incidental findings appearing. This review focuses on empirical research on the ethical issues involved.

Secondary variants--in defense of a more fitting term in the incidental findings debate.

New genetic technologies are capable of returning far more information than the single answer to the single question posed when conducting a given genetic test. Genetics contexts consequently stand on the brink of an explosion of what have traditionally been called 'incidental findings'. However, the continued use of this term is controversial.

To tell or not to tell? A systematic review of ethical reflections on incidental findings arising in genetics contexts.

Any test that produces visual images or digital or genetic sequences will tend to produce incidental findings because more will be visible than what was originally sought. We conducted a systematic review of the ethical reasons presented in the literature for and against the disclosure of incidental findings arising in clinical and research genetics contexts. A search of electronic databases resulted in 13 articles included for systematic review.

Invasive hyphal growth: an F-actin depleted zone is associated with invasive hyphae of the oomycetes Achlya bisexualis and Phytophthora cinnamomi.

We have compared F-actin patterns in invasive and non-invasive oomycete hyphae. In Achlya bisexualis an F-actin depleted zone is present in 70% of invasive but only 9% of non-invasive hyphae. In Phytophthora cinnamomi these figures are 74 and 20%, respectively.