Rectifying or Reinforcing? The (In)Equity Implications of Recontacting Practices in Genomic Medicine.

The practice of recontact in genomic medicine has the power to help rectify long-standing inequities in genetic testing. However, if not delivered systematically, recontacting practices also have the potential to reinforce these same inequities. Recontact, which occurs when contact between a clinician and patient is reinitiated after a relationship has ended, is often in search of or in response to updated interpretation or results.

Rare Disease Education Outside of the Classroom and Clinic: Evaluation of the RARE Compassion Program for Undergraduate Medical Students.

Launched in 2014, the RARE Compassion Program is the first international educational program to pair medical students with rare disease patients in order to enhance exposure to and comfort with rare diseases. As part of ongoing quality improvement, this study retrospectively reviewed four years of participant registration data to conduct a program evaluation of the RARE Compassion Program between 2014-2018. During the study period, there were 334 student participants, representing 67.

Systematic review of diffuse hemispheric glioma, H3 G34-mutant: Outcomes and associated clinical factors.

Background: A comprehensive review and description of the clinical features that impact prognosis for patients with diffuse hemispheric glioma, H3 G34-mutant (G34-DHG) is needed. Understanding survival and prognostic features is paramount for clinical advancements and patient care.

Methods: PubMed, Embase, and Google Scholar were searched for English articles published between January 1, 2012 and June 30, 2021.

A Rare Hemoglobin Variant (β51Pro → His) Causing Misleading Measurements of Hemoglobin A.

Glycated hemoglobin A (HbA) is considered the standard of care for the testing and monitoring of diabetes. Its ability to accurately reflect glycemia, however, is imperfect. Hemoglobin variants-mutant forms of hemoglobin caused by genetic variation present in 7% of the population-are known to adversely affect the ability of HbA measurement to reflect glycemic control.

Revisiting Risk and Benefit in Early Oncology Trials in the Era of Precision Medicine: A Systematic Review and Meta-Analysis of Phase I Trials of Targeted Single-Agent Anticancer Therapies.

Purpose: Phase I trials are a crucial step in the evaluation of new cancer therapies. Historically, low rates of response (5%) and comparably high rates of death from toxicities (0.5%) have contributed to debates on the ethics and orientation of these trials.

Secondary findings in inherited heart conditions: a genotype-first feasibility study to assess phenotype, behavioural and psychosocial outcomes.

Disclosing secondary findings (SF) from genome sequencing (GS) can alert carriers to disease risk. However, evidence around variant-disease association and consequences of disclosure for individuals and healthcare services is limited. We report on the feasibility of an approach to identification of SF in inherited cardiac conditions (ICC) genes in participants in a rare disease GS study, followed by targeted clinical evaluation.

From Genotype to Phenotype.

Genomic variants associated with inherited cardiac conditions yet detected incidentally (‘secondary findings’) are likely to arise with increasing frequency as genome sequencing transitions into clinical practice. Since genotyping has until recently been directed by clinical diagnosis, assessment and management of individuals found to harbour such a variant as a secondary finding is unclear. Here we illustrate some diagnostic and psychosocial complexities of inherited cardiac condition secondary findings, exemplified by disclosure of a pathogenic variant in , associated with long QT syndrome, to a healthy male enrolled in diagnostic genome sequencing as an unaffected relative.

Views of rare disease participants in a UK whole-genome sequencing study towards secondary findings: a qualitative study.

With large-scale genome sequencing initiatives underway, vast amounts of genomic data are being generated. Results-including secondary findings (SF)-are being returned, although policies around generation and management remain inconsistent. In order to inform relevant policy, it is essential that the views of stakeholders be considered-including participants who have made decisions about SF since the wider debate began.

"Not pathogenic until proven otherwise": perspectives of UK clinical genomics professionals toward secondary findings in context of a Genomic Medicine Multidisciplinary Team and the 100,000 Genomes Project.

PurposeApproaches to secondary findings in genome sequencing (GS) are unresolved. In the United Kingdom, GS is now routinely available through the 100,000 Genomes Project, which offers participants feedback of limited secondary findings.MethodsIn Oxford, a Genomic Medicine Multidisciplinary Team (GM-MDT) governs local access to GS, and reviews findings.

Expect the unexpected: screening for secondary findings in clinical genomics research.

Background: Due to decreasing cost, and increasing speed and precision, genomic sequencing in research is resulting in the generation of vast amounts of genetic data. The question of how to manage that information has been an area of significant debate. In particular, there has been much discussion around the issue of 'secondary findings' (SF)-findings unrelated to the research that have diagnostic significance.

Insights from early experience of a Rare Disease Genomic Medicine Multidisciplinary Team: a qualitative study.

Whole-exome/whole-genome sequencing (WES/WGS) has the potential to enhance genetic diagnosis of rare disease, and is increasingly becoming part of routine clinical care in mainstream medicine. Effective translation will require ongoing efforts in a number of areas including: selection of appropriate patients, provision of effective consent, pre- and post-test genetic counselling, improving variant interpretation algorithms and practices, and management of secondary findings including those found incidentally and those actively sought. Allied to this is the need for an effective education programme for all members of clinical teams involved in care of patients with rare disease, as well as to maintain public confidence in the use of these technologies.

Stakeholder views on secondary findings in whole-genome and whole-exome sequencing: a systematic review of quantitative and qualitative studies.

Purpose: As whole-exome sequencing (WES) and whole-genome sequencing (WGS) move into routine clinical practice, it is timely to review data that might inform the debate regarding secondary findings (SF) and the development of policies that maximize participant benefit.

Methods: We systematically searched for qualitative and quantitative studies that explored stakeholder views on SF in WES/WGS. Framework analysis was undertaken to identify major themes.

Complete mitochondrial genomes for Icelus spatula, Aspidophoroides olrikii and Leptoclinus maculatus: pan-Arctic marine fishes from Canadian waters.

Three Arctic marine fishes Icelus spatula, Aspidophoroides olrikii and Leptoclinus maculatus have been identified as target species for investigating the effects of ocean warming on population patterns in high-latitude marine habitats around Canada. In preparation for this research, we have resolved whole mitochondrial genome sequences of 16 384, 17 200 and 16 384 bp for each species, respectively. GC content for each species was 47.

Phenotypic overlap between familial exudative vitreoretinopathy and microcephaly, lymphedema, and chorioretinal dysplasia caused by KIF11 mutations.

Importance: Retinal detachment with avascularity of the peripheral retina, typically associated with familial exudative vitreoretinopathy (FEVR), can result from mutations in KIF11, a gene recently identified to cause microcephaly, lymphedema, and chorioretinal dysplasia (MLCRD) as well as chorioretinal dysplasia, microcephaly, and mental retardation (CDMMR). Ophthalmologists should be aware of the range of presentations for mutations in KIF11 because the phenotypic distinction between FEVR and MLCRD/CDMMR portends management implications in patients with these conditions.

Objective: To identify gene mutations in patients who present with a FEVR phenotype and explore the spectrum of ocular and systemic abnormalities caused by KIF11 mutations in a cohort of patients with FEVR or microcephaly in conjunction with chorioretinopathy or FEVR.

Gyrodactylus laevisoides n. sp. (Monogenea: Gyrodactylidae) infecting northern redbelly dace Phoxinus eos Cope (Cyprinidae) from Nova Scotia, Canada.

Gyrodactylus laevisoides n. sp. is described from the gill rakers of red belly dace, Phoxinus eos Cope (Cyprinidae), from Nova Scotia, Canada.