The development and evaluation of a nationwide training program for oncology health professionals in the provision of genetic testing for ovarian cancer patients.

BACKGROUND: BRCA1/2 mutation status has increasing relevance for ovarian cancer treatments, making traditional coordination of genetic testing by genetic services unsustainable. Consequently alternative models of genetic testing have been developed to improve testing at the initial diagnosis for all eligible women. METHODS: A training module to enable mainstreamed genetic testing by oncology healthcare professionals was developed by genetic health professionals. Oncology healthcare professionals completed questionnaires before and 12 months post-training to assess perceived skills, competence and barriers to their coordinating genetic testing for women with high-grade non-mucinous epithelial ovarian cancer. Genetic health professionals were surveyed 12 months post-training to assess perceived barriers to implementation of mainstreaming. RESULTS: 185 oncology healthcare professionals were trained in 42 workshops at 35 Australasian hospitals. Of the 273 tests ordered by oncology healthcare professionals post-training, 241 (93.1%) met national testing guidelines. The number of tests ordered by genetic health professionals reduced significantly (z = 45.0, p = 0.008). Oncology healthcare professionals' perceived barriers to mainstreamed testing decreased from baseline to follow-up (t = 2.39, p = 0.023), particularly perceived skills, knowledge and attitudes. However, only 58% reported either 'always' or 'nearly always' having ordered BRCA testing for eligible patients at 12 months, suggesting oncology healthcare professionals' perceived barriers were not systematically addressed through training. CONCLUSIONS: Oncology healthcare professionals have demonstrated a willingness to be involved in the provision of genetic testing in a mainstreaming model. If oncology services are to hold responsibility for coordinating genetic testing, their readiness will require understanding of barriers not addressed by training alone to inform future intervention design.

Tricho-hepatic-enteric syndrome (THES) without intractable diarrhoea.

Tricho-hepatic-enteric syndrome (THES) is a genetically heterogeneous rare syndrome (OMIM: 222470 (THES1) and 614602 (THES2)) that typically presents in the neonatal period with intractable diarrhoea, intra-uterine growth retardation (IUGR), facial dysmorphism, and hair and skin changes. THES is associated with pathogenic variants in either TTC37 or SKIV2L; both are components of the human SKI complex, an RNA exosome cofactor. We report an 8 year old girl who was diagnosed with THES by the Undiagnosed Disease Program-WA with compound heterozygous pathogenic variants in SKIV2L. While THES was considered in the differential diagnosis, the absence of protracted diarrhoea delayed definitive diagnosis. We therefore suggest that SKIV2L testing should be considered in cases otherwise suggestive of THES, but without the characteristic diarrhoea. We expand the phenotypic spectrum while reviewing the current knowledge on SKIV2L.

The future in clinical genetics: affective forecasting biases in patient and clinician decision making.

When clinicians facilitate and patients make decisions about predictive genetic testing, they often base their choices on the predicted emotional consequences of positive and negative test results. Research from psychology and decision making suggests that such predictions may often be biased. Work on affective forecasting-predicting one's future emotional states-shows that people tend to overestimate the impact of (especially negative) emotional events on their well-being; a phenomenon termed the impact bias. In this article, we review the causes and consequences of the impact bias in medical decision making, with a focus on applying such findings to predictive testing in clinical genetics. We also recommend strategies for reducing the impact bias and consider the ethical and practical implications of doing so.

Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice.

BACKGROUND: Microarray genome analysis is realising its promise for improving detection of genetic abnormalities in individuals with mental retardation and congenital abnormality. Copy number variations (CNVs) are now readily detectable using a variety of platforms and a major challenge is the distinction of pathogenic from ubiquitous, benign polymorphic CNVs. The aim of this study was to investigate replacement of time consuming, locus specific testing for specific microdeletion and microduplication syndromes with microarray analysis, which theoretically should detect all known syndromes with CNV aetiologies as well as new ones. METHODS: Genome wide copy number analysis was performed on 117 patients using Affymetrix 250K microarrays. RESULTS: 434 CNVs (195 losses and 239 gains) were found, including 18 pathogenic CNVs and 9 identified as "potentially pathogenic". Almost all pathogenic CNVs were larger than 500 kb, significantly larger than the median size of all CNVs detected. Segmental regions of loss of heterozygosity larger than 5 Mb were found in 5 patients. CONCLUSIONS: Genome microarray analysis has improved diagnostic success in this group of patients. Several examples of recently discovered "new syndromes" were found suggesting they are more common than previously suspected and collectively are likely to be a major cause of mental retardation. The findings have several implications for clinical practice. The study revealed the potential to make genetic diagnoses that were not evident in the clinical presentation, with implications for pretest counselling and the consent process. The importance of contributing novel CNVs to high quality databases for genotype-phenotype analysis and review of guidelines for selection of individuals for microarray analysis is emphasised.