Adolescents' implicit and explicit attitudes toward their peers with genetic conditions.

INTRODUCTION: Previous research has demonstrated that children lacking knowledge about genetic disorders may have harmful attitudes toward people with disabilities, but disability awareness can successfully modify these attitudes. We explored adolescents' implicit and explicit attitudes toward peers with genetic conditions to determine whether improved genetics/genomics literacy can mitigate the impact of ableism in this population. METHODS: English-speaking adolescents (10-18 years) from British Columbia were invited to complete a Disability Attitudes Implicit Association Test (DA-IAT) and participate in a semi-structured focus group centering on a fictionalized vignette about an adolescent with Down syndrome. We used pragmatism as an analytical paradigm. Descriptive and inferential statistics were used to analyze DA-IAT and sociodemographic data; phronetic iterative analysis with constant comparison as a coding strategy for transcripts; and interpretive description to develop a conceptual model. RESULTS: Twenty-two adolescents completed the DA-IAT and participated in one of four focus groups. Participants had a statistically significant implicit preference for non-disabled people (D-score = 0.72, SD = 0.44; t = 7.18, p < .00001). They demonstrated greater diversity in their explicit attitudes during the focus groups. Although participants articulated a positive attitude toward improved genetics education, results demonstrate their belief that social and personal interactions with disabled peers would be essential to address negative perceptions. CONCLUSIONS: This study lays important groundwork to understand, explain, and influence the negative attitudes of adolescents toward individuals with disabilities. Findings will be used to inform the design of interventions that address biased perceptions of people with genetic disorders, with the goal of reducing prejudices and improving social interactions.

Exploring genetic counselors' experiences with non-paternity in clinical settings.

Non-paternity (NP) is a challenging dilemma faced by genetics providers and there is little consensus on whether this finding should be disclosed. Discussions in the literature are highly theoretical, with limited research regarding how disclosure decisions are enacted in practice. We explored genetic counselors' (GCs) clinical experiences with NP to understand if, how, and why this finding is communicated. Our semi-structured interviews with genetic counselors in the United States and Canada were analyzed using reflexive thematic analysis to analyze data inductively, describe themes, and present a meaningful interpretation of the data. Eighteen participants who responded to list-serv messages were interviewed. Our framework describes five salient themes: (1) GC-lab relationship: the GCs awareness of laboratory processes such as quality control metrics that can uncover NP findings and the way in which a finding of NP was disclosed by the laboratory had an impact on disclosure decisions. This triggered a decision-making trajectory that involved (2) consultation, (3) ethical reasoning, and (4) practical constraints. GCs frequently consulted other professionals during decision-making. These conversations impacted disclosure decisions with some consultations carrying greater weight than others. GCs weighed moral concepts of patient autonomy, medical relevance, and preventing harm to rationalize decisions. Access to patients and documentation requirements often dictated how disclosure occurred. Finally, once a decision had been made and enacted, GCs used the experience to reconsider their approach to (5) consenting in future cases, with some GCs altering their pre-test counseling to always include a discussion of NP. Although NP scenarios are frequently unique in context, our findings demonstrate several common decision-making factors GCs harness to navigate the identification of NP through clinical genetic testing.

A novel online genomic counseling and variant interpretation certificate: Learning design, learning analytics, and evaluation.

In this paper we describe the analysis, planning, design, development, implementation and evaluation of a new online Graduate Certificate in Genomic Counselling and Variant Interpretation (GCGCVI) at The University of British Columbia (UBC). Genetic counselling is now a prerequisite for diagnostic genomic testing in many countries, demanding that genetic counselling practitioners have up-to-the-moment genomic counselling skills and knowledge. Current practitioners reported a desire for more training in this rapidly developing field: our international survey revealed substantial interest in online continuing education addressing themes such as testing and clinical bioinformatics, applied variant interpretation, evidence-based genomic counselling, and other emerging genomic topics. However, our market analysis found no post-graduate program globally that offered such training. To fill this gap, our oversight team of genetic counsellors and geneticists therefore guided development of curriculum and materials, and online learning specialists developed rigorous interactive asynchronous online graduate courses through collaboration with subject matter experts, following best practices in online learning design. Since launch in September 2020, we have gathered learner feedback using surveys and focus groups, and we have used learning analytics to understand how learners engaged with each other and with course materials. Together, these have helped us understand learner behaviour and guide the continuous process of design improvement to support the learning goals of this audience of professional learners. Our courses have been reviewed and approved by the UBC Faculty of Medicine, UBC Senate, and the Province of British Columbia Ministries of Advanced Education and Health, and assessed by the National Society of Genetic Counselors (NSGC, USA) and the Canadian Association of Genetic Counsellors (CAGC) to enable learners to receive North American continuing education credits. To date, 151 individuals from 18 countries have succeeded in one or more course and 43 have completed the entire certificate.

Genetic counselors' research dissemination practices and attitudes.

Benefits have been demonstrated to disseminating aggregate research results to all relevant audiences, including study participants. Despite this, many health researchers face barriers in dissemination to broad audiences and returning aggregate results to participants is not commonly practiced. Due to their research presence and training in communication, genetic counselors can lead in implementing best practices in this area. We explored genetic counselors' current practices and opinions regarding educating study participants and wider audiences of research findings. We distributed a survey of 32 multiple-choice and open-ended questions to National Society of Genetics Counselors (NSGC) and Canadian Association of Genetic Counsellors (CAGC) members. Most respondents (90.1%, n = 128/142) identified with a responsibility to disseminate their research findings to a broad audience and identified several associated benefits. All respondents saw value in communicating aggregate results to study participants, although over half (53.2%, n = 66/124) had never done so. Genetic counselors reported resource and knowledge barriers to research dissemination. Despite expertise in education and communication, genetic counselors face similar barriers as other researchers toward broad dissemination of research. Formal training and professional guidelines specific to research dissemination practices will equip genetic counselors to reach broader audiences and maximize the impact of research findings.

Considerations for the use of qualitative methodologies in genetic counseling research.

An abundance of qualitative research is being conducted within the genetic counseling field. As this area of research expands, many within our community are "learning through doing", an approach which is practical, but may lack theoretical grounding. This can result in study outputs that do not have the sort of utility for informing clinical practice that is the hallmark of excellent clinical qualitative research. Furthermore, our alignment as a discipline within the health sciences, which still tends to favor quantitative approaches, means that we may often be obliged to justify the use of qualitative methodologies, especially when we intend to use the findings for informing clinical practice. We aim to address these issues by providing guidance about how we, individually and collectively, might think about what excellent qualitative research can look like in our field. In addition to providing information and resources about current best-practices, we discuss how quality can be ensured and evaluated. We seek to legitimize the idea of developing a philosophy of research in pursuit of establishing genetic counseling as an academic discipline. We argue that the principles, ethics, values, and practices of genetic counseling are sufficiently unique that establishing a discipline-specific qualitative research framework is not only warranted, but essential. Ultimately, we hope that this paper can serve as a launching point from which additional discussion about qualitative research can emanate as we strive towards the elevation of this form of inquiry in our field.

The experiences of adolescent siblings of children with rare genetic conditions: "It's made me who I am".

Childhood genetic conditions impact not only the child who is diagnosed but also the day-to-day lives of all members of a family. However, our understanding of the perspectives and needs of unaffected adolescents in families affected by rare genetic conditions is limited. To address this gap, we conducted semi-structured interviews with 10 participants aged 14-20 years, all of whom had a sibling with a rare genetic condition. An interpretive description approach was used to develop a framework that described how participants' experiences of having a sibling with a rare genetic condition shaped the formation of their identity. This experience influenced identity formation both directly, and indirectly through four other phenomena: (1) normalization, of both their own experiences and their siblings' differences; (2) knowledge seeking, regarding their sibling's condition and what uncertainties remained; (3) caretaking, which limited some opportunities and was associated with uncertainty around the future; and (4) social experience, including their relationship with their affected sibling, with their peers, and with the rest of their family participants felt that they were isolated and lacked appropriate supports. The results of this study can help to inform a family-centered approach to genetic counseling and highlight the importance of tailored supports for this population.

Implementing genomics in the neonatal period: An assessment of parental decision making and anxiety.

As uptake of rapid genome sequencing (GS) in the neonatal period steadily increases, a clinical genetics service that is optimized to the needs of parents becomes increasingly important. We aimed to investigate factors that influence decision making about rapid GS by parents of infants admitted to neonatal intensive care units (NICU) and explore their experiences of decisional conflict and anxiety during this time. Parents of neonates suspected of having a genetic disorder and offered rapid GS in the NICU completed a questionnaire measuring experience with GS counseling, decisional conflict, and anxiety level. Our results demonstrate that despite a largely positive GS experience (70%; 21/30) among the survey respondents, 50.0% (14/28) experienced moderate to severe anxiety measured using the GAD-7 scale, and 34.6% (9/26) experienced decisional conflict measured using the SURE scale. We also showed that prematurity may be a modifier of anxiety in this group of parents and although not statistically significant, distance lived away from the hospital site could have practical significance. Open-ended responses to survey questions highlighted that feeling overwhelmed, the types of engagements parents had with healthcare providers, and the timing of information provision also influenced parental decision making in this setting. We suggest that the GAD-7 scale for generalized anxiety and SURE scale for decisional conflict could be incorporated by genetic counselors into routine care of parents of neonates who have been offered rapid GS to identify those who may need additional support (resources, information, or psychological). These tools may inform ways that communication between patients and providers can be improved and enhanced and clinical genetics services in the NICU can be optimized. We suggest that integrating genetic counselors into the NICU care team could increase access for this population and ensure delivery of optimized patient education and counseling.

Experiences With Genetic Counseling, Testing, and Diagnosis Among Adolescents With a Genetic Condition: A Scoping Review.

Importance: The number of adolescents who are diagnosed with a genetic disorder is increasing as genome sequencing becomes the standard of clinical diagnostic testing. However, the experience of receiving a diagnosis of a genetic condition has not been extensively studied in adolescents. Objective: To identify how adolescents with a genetic condition engage with genetic or genomic counseling services as well as interpret, adapt to, and experience their diagnosis. Evidence Review: A literature search of MEDLINE, Embase, CINAHL, and PsycINFO was undertaken. Articles (primary literature, knowledge syntheses, and gray literature) in English that investigated the experiences of adolescents between 10 and 19 years of age who received genetic or genomic counseling were included. Data were extracted from 45 eligible articles and analyzed descriptively. Findings: A total of 45 studies were included, most of which were quantitative in nature (21 of 45 [47%]) and conducted in the US (n = 13), followed by the UK (n = 8), Australia (n = 8), and Canada (n = 6). A total of 29 distinct monogenic disorders were investigated. Sample sizes ranged from 1 to 930, with a median of 23 participants, and the year of publication ranged from 1977 to 2019. Included studies addressed all aspects of genetic counseling, but a preponderance of articles assessed knowledge about genetic conditions (n = 17) and challenges of communication within families (n = 16). Fewer articles addressed the experiences of adolescents adapting to their genetic conditions (n = 8) and the genetic counseling process (n = 4). Only 1 study addressed any aspect of genetic counseling in relation to genome sequencing. Conclusions and Relevance: This scoping review found that most of the included studies focused on adolescents' knowledge about their genetic condition and communication about genetic risks, whereas fewer studies explored their adaptation to the condition and the genetic counseling process. A systematic reconsideration of the genetic counseling process may be undertaken to provide an evidence-informed health care service that is tailored to the needs of this adolescent population.

Far and wide: Exploring provider utilization of remote service provision for genome-wide sequencing in Canada.

BACKGROUND: In Canada, funding for genome-wide sequencing (GWS; exome and whole genome) is provincially regulated. We characterized the uptake of GWS by genetics health professionals (GHPs) across Canada and describe how they use remote technologies for patient access to GWS and genomic counseling. METHODS: We distributed a survey to 574 Canadian GHPs addressing: GWS use, remote technologies (e.g., telephone, videoconferencing) for GWS and provider opinions regarding these technologies. Data were summarized using descriptive statistics. Associations between variables were evaluated using Chi-square and Fisher's Exact tests for categorical data, and t-tests or Mann-Whitney U tests for continuous data. RESULTS: Of 116 GHPs, 50% reported using GWS in the last year and 57% of GWS users reported using remote technologies. Clinical geneticists who did not use GWS reported lack of provincial funding as the principal reason. Remote technologies were most commonly used for informed consent and results, and rarely used for initial consultations. Average wait times for a GWS appointment were shorter for remote appointments (mean 44.2 (SD 40.2) weeks) than for in-person (mean 58.2 (SD 42.9), p = 0.036). CONCLUSION: The use of GWS varied across Canada, professional designation, and discipline. Funding remains a barrier to GWS access. Remote technologies increase patient access with reduced wait times.

Review of 10 years of preimplantation genetic diagnosis in South Africa: implications for a low-to-middle-income country.

PURPOSE: To evaluate the preimplantation genetic diagnosis (PGD) service, for the period of January 2006 to December 2016, through a South African academic and diagnostic Human Genetics Unit, and to assess the outcomes and cost of PGD. METHODS: A retrospective review of PGD files available at the Human Genetics Unit was performed. Data was collected from genetic counseling, fertility, and PGD-specific records. RESULTS: Amongst the 22 couples who had PGD, 42 in vitro fertilisation cycles were completed with 228 embryos biopsied and included in the analysis. Most (59%) of the conditions for which PGD was requested were autosomal recessive. Of the biopsied embryos, 71/228 (31.1%) were suitable for transfer and 41/71 (57.7%) were transferred. Of these, 14/41 (34.0%) successfully implanted and 11/14 (78.6%) resulted in a liveborn infant. The clinical pregnancy rate per embryo transfer was 29.3%. Overall, 10/22 (45.5%) couples had a successful cycle resulting in a liveborn infant. On average, one cycle of PGD costs USD 9525. CONCLUSIONS: This is the first study to assess the success rates and the cost of PGD in South Africa and provides evidence for the feasibility in a low-to-middle-income country. The success rates in this sample are comparable to those achieved globally. South Africa has the infrastructure and expertise to provide PGD; the limiting factor is the lack of funding initiatives for PGD. Although the sample size was small, the findings from this study will enable genetic counselors to offer couples in South Africa evidence-based and locally accurate information regarding outcomes, success rates, and costs.

Biallelic BRCA2 mutations in two black South African children with Fanconi anaemia.

Fanconi anaemia (FA) is a genotypically and phenotypically heterogeneous genetic condition, characterized cytogenetically by chromosomal instability and breakage secondary to impaired DNA repair mechanisms. Affected individuals typically manifest growth restriction and congenital physical abnormalities and most progress to hematological disease including bone marrow aplasia. A rare genetic subtype of FA (FA-D1) is caused by biallelic mutations in the BRCA2 gene. Affected individuals manifest severe congenital anomalies and significant pigmentary changes and are additionally at risk for early onset leukemia and certain solid organ malignancies, including Wilms tumors and brain tumors. Parents of affected individuals are obligate carriers for heterozygous BRCA2 mutations and are thus potentially at risk for adult onset cancers which fall within the hereditary breast and ovarian cancer spectrum. We present two cases of black South African patients with FA diagnosed with biallelic BRCA2 mutations and discuss the phenotypic consequences and implications for them and their families. Recognition of this severe end of the phenotypic spectrum of FA is critical in allowing for confirmation of the diagnosis as well as cascade screening and appropriate care of family members.

Breast cancer in high-risk Afrikaner families: Is BRCA founder mutation testing sufficient?

BACKGROUND: Germline pathogenic mutations in cancer susceptibility genes result in inherited cancer syndromes. In the Afrikaner population of South Africa (SA), three founder mutations in the BRCA genes that lead to hereditary breast and ovarian cancer syndrome (HBOCS) have been identified. OBJECTIVES: To investigate the uptake and type of molecular testing performed on patients for HBOCS, to determine the prevalence of the three Afrikaner founder BRCA mutations as well as non-founder BRCA mutations in the study population, and to analyse the utility of two mutation prediction models (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and Manchester scoring method) in assisting with the decision for the most cost-effective testing option. METHODS: A retrospective file review was performed on counsellees of self-reported Afrikaner ancestry from Johannesburg, SA (2001 - 2014), with a personal or family history of breast and/or ovarian cancer. Demographic and family history information was recorded and Manchester and BOADICEA scores were calculated for each patient. RESULTS: Of 86 unrelated counsellees whose files were reviewed, 54 (62.8%) underwent BRCA genetic testing; 18 (33.3%) tested positive for a mutation, and 14 of these (77.8%) for an Afrikaner founder mutation. Twelve counsellees had the BRCA2 c.7934delG mutation. Four non-founder mutations were identified. BOADICEA scores were significantly higher in counsellees who tested positive for a mutation than in those who tested negative. CONCLUSIONS: Founder mutation testing should be performed as a first-line option. BOADICEA is very useful in identifying counsellees at high risk for a BRCA mutation and also assists with the decision to pursue further testing following a negative founder mutation result. These findings assist in guiding an informed genetic counselling service for at-risk individuals with an Afrikaner background.

MYOC mutations in black south african patients with primary open-angle glaucoma: genetic testing and cascade screening.

BACKGROUND: Primary Open Angle Glaucoma (POAG) is an important cause of irreversible blindness in South Africa. Mutations in the MYOC gene are important in monogenic POAG. This study aimed to characterize potentially pathogenic MYOC mutations in this population. MATERIALS AND METHODS: Self-identified black South African POAG patients (215) and unaffected control participants (214) had ophthalmological examinations and DNA extraction. Potentially pathogenic MYOC variants were genotyped in the study population. Family members of participants with the mutations were screened for glaucoma clinically and for the mutations using Sanger sequencing. RESULTS: The following mutations were genotyped: Gly374Val (2 POAG patients), Lys500Arg (3 POAG patients) and Tyr453del (5 POAG patients). None of the relatives screened for Gly374Val had the mutation or POAG. The Lys500Arg mutation did not co-segregate with the disease in an affected family. The Tyr453del mutation co-segregated with the disease, but demonstrated incomplete penetrance. POAG patients with the Tyr453del mutation had adult-onset POAG with high intraocular pressures and advanced cupping. CONCLUSIONS: Overall, 3.3% of black South Africans with POAG have a Gly374Val or Tyr453del MYOC mutation. The Tyr453del mutation is incompletely penetrant. That the mutation is necessary but insufficient introduces a counseling dilemma. Mutation screening can, however, identify high-risk individuals who can be monitored to detect early signs of the disease. The Gly374Val mutation is predicted to be damaging to MYOC. The Lys500Arg mutation is predicted to be benign and tolerated. This study has important implications for the management and counseling of black South African patients with POAG and their families.

Fanconi anaemia in black South African patients heterozygous for the FANCG c.637-643delTACCGCC founder mutation.

BACKGROUND: Fanconi anaemia (FA) is an autosomal recessive, genetically heterogeneous disorder, characterised by interstrand crosslink-induced chromosome breaks, congenital abnormalities and predisposition to malignancies. It has a prevalence of about 1/40 000 in black South Africans (SAs). A founder mutation in the FANCG gene occurs in the homozygous state in 77.5% of southern African blacks. OBJECTIVE: To locate additional pathogenic mutations in the FANCG gene of black FA patients who were heterozygous for the founder mutation. Methods. Further mutation analysis of the FANCG gene was undertaken in 7 patients clinically suspected of having FA. The parents of two of the patients were tested for the presence of the founder mutation to determine true heterozygosity in the patients. To clarify whether or not previously unreported variants were pathogenic, 58 random black SA individuals were screened. RESULTS: Three novel single base pair deletions, resulting in frameshift mutations (c.247delA, c.179delT and c.899delT) were identified in 3/7 patients. A fourth patient was found to have a single base substitution resulting in a splice site mutation (c.1636+1G>A). The remaining three patients were not found to harbour any pathogenic mutations. Two non-pathogenic variants were also identified among the seven patients. CONCLUSION: The results of this small sample suggest that a second common mutation in the FANCG gene is unlikely in this population. However, FANCG sequencing should be performed on patients heterozygous for the common founder mutation to attempt to confirm their diagnosis.

Testing for haemoglobinopathies in Johannesburg, South Africa: a 30-year review.

BACKGROUND: Haemoglobinopathies are seen mostly in regions where malaria occurs or has occurred, but population migration has resulted in affected individuals being identified in many countries globally. The first molecular genetics services for diagnostic testing and prenatal diagnosis were established, both worldwide and in South Africa (SA), for haemoglobinopathies. OBJECTIVE: To analyse the diagnostic service offered by the Division of Human Genetics, National Health Laboratory Service and University of the Witwatersrand, from 1983 to 2012. METHODS: A retrospective file analysis (N=1 249) was performed for all individuals who had molecular genetic testing for α-thalassaemia, ß-thalassaemia and sickle cell anaemia to examine indications for testing, population origins of patients and molecular genetics findings. RESULTS: The α-thalassaemia testing was requested predominantly to explain microcytic hypochromic haematological indices. Five α-globin deletions were identified, the most common being the -α3.7, in individuals of different ethnicities. For ß-thalassaemia and sickle cell anaemia, most testing was performed for prenatal diagnosis purposes. For sickle cell anaemia, most prenatal tests were requested by African families. The ß-thalassaemia families were mostly of Indian or Mediterranean origin. The most common mutation identified in all Indian groups was IVS1 nt5 (G>C) (c.92+5G>C) and in individuals from the Mediterranean, IVS1 nt110 (G>A) (c.93-21G>A). CONCLUSION: The molecular genetics service for haemoglobinopathies in SA is comprehensive and specific to the needs of local ethnic groups. Clinically significant haemoglobinopathies occur at significant frequencies in specific high-risk ethnic groups. Appropriate screening programmes should be initiated so that genetic counselling and reproductive options can be offered.