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Aim: This paper determines the polymorphism distribution of the VDR BsmI gene in 350 patients and provides medication recommendations for osteoporosis based on detection results. Materials & methods: Chi-square tests compared genotype and allele frequencies with other populations. Results: Genotype frequencies were 91.66 bb, 8.72 Bb and 0.21% BB, with allelic frequencies of 95.43 b and 4.57% B, adhering to Hardy–Weinberg equilibrium. These findings suggest that VDR gene polymorphisms, particularly at the BsmIlocus, play an essential role in bone health and osteoporosis treatment. Genotype-based drug selection reduced adverse reactions from 14 to two cases. Conclusion: These findings improve clinical treatment efficacy and guide rational drug use for osteoporosis patients. Article highlights Objective To determine the polymorphism distribution of the vitamin D receptor (VDR) BsmI locus gene in osteoporosis patients and provide medication recommendations. Methods Genetic testing of 350 patients for VDR BsmI gene polymorphisms, comparison of genotype and allele frequencies, and assessment of the impact on drug selection. Significance Understanding the role of VDR gene polymorphisms in bone health and treatment response, and the potential for genotype-based drug selection. Results Genotype distribution: The study identified three genotypes at the BsmI locus: bb (91.66%), Bb (8.72%) and BB (0.21%), with allele frequencies of 95.43% for b and 4.57% for B. This distribution aligns with the Hardy–Weinberg equilibrium, indicating a representative sample. Comparison with other populations: The VDR gene allele frequencies in the Guangdong Han population significantly differ from those in South Asia, America, Europe and Africa but are similar to other East Asian populations. Impact on bone mineral density: There was no significant difference in bone mineral density T-scores before and after treatment across the different VDR genotypes, but patients with the b allele showed better responses to osteoporosis treatments, particularly with bisphosphonates. Adverse drug reactions (ADRs): before genetic testing, there were 14 ADRs, which reduced to only two cases post implementation, indicating improved treatment outcomes and reduced side effects through genotype-based drug selection. Conclusions The study supports the importance of genetic testing in guiding osteoporosis treatment as VDR gene polymorphisms, particularly at the BsmI locus, significantly influence treatment efficacy and the occurrence of ADRs. Genotype-based drug selection can improve clinical outcomes and minimize side effects. The findings suggest the need for further research on the distribution and impact of VDR BsmI locus polymorphism in different Chinese populations. Large-scale, multicenter studies are recommended to validate these results and enhance the precision of genotype-based drug recommendations. Integrating pharmacogenomics into clinical practice promises to improve the effectiveness of osteoporosis treatments, minimize adverse reactions, and advance personalized medicine, ultimately enhancing patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Genomic screening at population scale generates many ethical considerations. One is the normative role that people's preferences should play in determining access to genomic information in screening contexts, particularly information that falls beyond the scope of screening. We expect both that people will express a preference to receive such results and that there will be interest from the professional community in providing them. In this paper, we consider this issue in relation to the just and equitable design of population screening programs like reproductive genetic carrier screening (RGCS). Drawing on a pluralistic public health ethics perspective, we claim that generating and reporting information about genetic variants beyond the scope of the screening program usually lacks clinical, and perhaps personal, utility. There are both pragmatic and ethical reasons to restrict information provision to that which fits the stated purpose of the program. [ABSTRACT FROM AUTHOR]

Retinoblastoma (RB) is the most common primary intraocular malignant tumor in children. RB is mostly caused by biallelic mutations in RB1 and occurs in hereditary and non-hereditary forms according to the "two-hit" theory. RB1 mutations comprise point mutations, indels, large deletions, and duplications. Genetic testing is essential for the comprehensive treatment and management of patients with RB. The aim was to evaluate RB1 copy number variations (CNVs) using MLPA versus FISH assays in group of Egyptian patients with RB. 16.67% showed an RB1 deletion, abnormal methylation status, or both. Our results suggested MLPA is a fast, reliable, and powerful method and should be used as a first-line screening tool for detecting RB1 CNVs in patients with RB. Moreover, MLPA is advantageous as it evaluates the methylation status/inactivation of RB1, not possible by FISH. [ABSTRACT FROM AUTHOR]

Pharmacogenetics is the study of genetic variants in genes which may impact on the outcome of drug treatment, either through safety considerations (occurrence of adverse drug reactions or therapeutic failure) or altered drug pharmacokinetics. This paper provides a brief history of pharmacogenetics research in the Aotearoa/New Zealand context, and a commentary on our current state. Factors that have limited translation of pharmacogenetic knowledge into ou r healthcare system are considered, and possible solutions to these are proposed. Pharmacogenetic knowledge has long been invoked as a way to improve the safety and success of drug prescribing, but (with some notable exceptions) it has largely failed to achieve this promise. Several barriers to clinical implementation need to be overcome to ensure that pharmacogenetics becomes a key component of precision health for all people in Aotearoa/New Zealand. [ABSTRACT FROM AUTHOR]

Popular and scientific accounts of the molecularisation of cancer typically attribute it to advances in laboratory science, particularly molecular geneticists. However, historical research has indicated that clinical expertise input was often vital for advancing such work. The present paper reinforces that view. Looking in detail at British research into the molecular genetics of familial cancers during the 1980s and 1990s, it shows that that research, too, depended on crucial input from family cancer clinics. Moreover, the development of clinical services for familial cancers was in turn shaped by the demands of contributing to molecular genetic research. The paper concludes that accounts of the molecularisation of cancer that suppose a one-way transfer of knowledge and practice from laboratory to clinic misrepresent the complex interactions that were involved in molecularising familial cancers, and that were informed by the particular local and national circumstances in which they took shape. [ABSTRACT FROM AUTHOR]

In this era of personalisation a patient's molecular profile plays an increasingly central role in development and delivery of personalised medicine. This paper sets out to explore the sociocultural implications of mainstreaming BRCA genetic testing in the treatment of advanced ovarian cancer patients, who carry a BRCA1 or BRCA2 gene mutation. It draws on ethnographic research conducted by between April-June 2016 in a large tertiary London hospital. Participant observation was conducted across two sites. For the first two weeks participant observation was conducted in the traditional genetic testing setting in two separate clinics. From thereon, participant observation was conducted in the clinical encounters of treating patients in the ovarian cancer clinic. In addition, face-to-face interviews were conducted with medical oncologists who worked in the clinic. Contributing to the fields of cancer genetics, personalised medicine and medical material culture studies in medical anthropology the paper seeks to further discussions about the interactions and relationships unfolding between medical objects and subjects across the landscape of cancer care. It highlights the importance of clinic-based ethnography to examine the complexities of identities and technologies as they intersect with the themes of suffering and hope in new and contradictory ways for BRCA-positive patients with late-stage disease. The paper argues that a BRCA mutation is not only central to the political economy of hope but takes on a more materialist nature as it becomes an embodied practice that moves in and beyond the clinic. [ABSTRACT FROM AUTHOR]

This paper presents the first report of amyotrophic lateral sclerosis (ALS) kindred due to the KIF5A p.Arg1007Lys, a splice-altering variant. An index case was a 54-year-old male who developed progressive gait difficulty and imbalance followed by mild parkinsonism, spasticity, neuropathy, ataxia, and cognitive impairment with predominant subcortical frontal involvement. Brain MRI showed marked bilateral parietal lobes atrophy. Electromyography demonstrated chronic diffuse neurogenic changes. Due to the positive history of similar symptoms in his father and the diagnosis of ALS in 10 other family members, extensive genetic testing was pursued. Genetic screening for GRN, C9orf72, TARDBP, SOD1, FUS, MAPT mutations, and hereditary ataxia panel, was unremarkable. Whole-exome sequencing revealed c.3020G > A (p.Arg1007Lys) mutation in the KIF5A gene, later confirmed in two affected relatives. Similar to previous reports on KIF5A-related ALS, our index case, had a mild disease course with prolonged survival. However, as the rate of progression and survival time differed even among the same family members, other factors were probably at play. Additionally, our index case and his father displayed features overlapping ALS, spastic paraplegia, Charcot-Marie-Tooth disease type 2, and frontotemporal dementia. Therefore, we suggest considering KIF5A mutations in the differential diagnosis, particularly in the presence of overlapping features of spasticity, neuropathy, cerebellar ataxia, and dementia. [ABSTRACT FROM AUTHOR]

Influenza virus strains undergo genetic mutations every year and these changes in genetic makeup pose difficulties for effective vaccine selection. To better understand the problem it is important to statistically quantify the amount of genetic change between circulating strains from different years. In this paper, we propose the nonparametric crossmatch test applied to phylogenetic trees to assess the level of discrepancy between circulating flu virus strains between two years; the viruses being represented by a phylogenetic tree. The crossmatch test has advantages compared to parametric tests in that it preserves more information in the data. The outcome of the test would indicate whether the circulating influenza virus has mutated sufficiently in the past year to be considered as a new population of virus, suggesting the need to consider a new vaccine. We validate the test on simulated phylogenetic tree samples with varying branch lengths, as well as with publicly available virus sequence data from the 'Global Initiative on Sharing All Influenza Data' (GISAID: ) [ABSTRACT FROM AUTHOR]

Probit and Logit models are the most popular for binary disease statusing in genetic association studies. They are equally used and nearly exchangeable in the analysis of prospectively collected data. However, no strong inferences were made based on Probit models for the retrospectively collected case–control data, especially in the presence of random effects. This paper systematically investigates the performance of Probit mixed-effects models for case–control data. We find that the retrospective likelihood has a closed-form, which motivates the development of likelihood ratio tests for genetic association. Specifically, we developed four likelihood ratio tests based on whether the disease prevalence is completely unavailable, partly available, or completely available. We show that their limiting distribution without a genetic effect is an equal mixture of two chi-square distributions with degrees of freedom 1 and 2, respectively. Our simulations indicate that they can have a remarkable power gain against the popular Logit-model-based score tests, and the disease prevalence information can enhance the power of the likelihood ratio tests. After analyzing a Kenya malaria data, we found out that the proposed test produces a significant result on the association of the gene ABO with malaria, whereas the commonly used competitors fail. [ABSTRACT FROM AUTHOR]

Genetics is increasingly defining how we understand health and disease, affecting for some, their understanding of inherited disease, and the meaning of medical genetic information. When interpretations of hereditary conditions are determined, partly, by one's familial experience of heritable characteristics and partly by various other lived experiences, the meaning of genetics becomes highly personal. Through descriptions of stocks of knowledge, this paper describes findings from a qualitative study with a cohort of Black and Asian women with family and personal histories of cancer, about their interpretations of their genetic tests. We describe their interpretations as shaped by different experiences of biomedical practice as well as familial experiences of cancer and genetic testing; and we introduce a metaphor of "moving within a landscape," to show how those interpretations were created and influenced by various sources of knowledge and life experiences. [ABSTRACT FROM AUTHOR]

While much attention has gone towards ethical, legal, and social implications of direct-to-consumer genetic testing over the past decades, the rise of new forms of consumer omics has largely escaped scrutiny. In this paper, we analyze the product descriptions, promotional messages, terms of service, and privacy policies of five epigenetic and seven microbiomic testing companies. The advent of such tests online represents a significant shift in consumer omics, from a focus on inherited molecules with genetic tests, to broader interest for information about the lives of individuals, such as chronological and biological age, exposures, and lifestyle. Building on previous literature about direct-to-consumer genetic testing, and taking this shift into account, we identify limitations, gaps and inconsistencies in current practices and policies of the new companies. Best practice standards and regulations applicable across different omic sample and data types is a necessary first step in the promotion of responsible consumer omics. [ABSTRACT FROM AUTHOR]

Drawing on data from semi-structured interviews conducted in Singapore, Canada, and the United States, this paper shows that biomedical experts are deeply concerned about the shortcomings of the biomedical model of health. Precision public health, when anchored in genomics, can be considered a twenty-first century version of the medical model of health, which originated from nineteenth century germ theory. First, concerns regarding the adoption of genetic testing to identify disease susceptibility, and limitations of genome-based disease prevention exist. This includes limited evidence of the utility of screening measures in reducing mortality, lack of reimbursement for genetic screening, negative implications of genetic screening, and limitations of race/ethnicity-based genetic screening. Second, there are also concerns regarding the treatment of diseases, particularly the management of the costs of treatment and genetic testing in the context of national public health systems. Ultimately, it was found that healthcare-related inequities can be reduced in a universal, publicly funded, single-payer healthcare setting. These findings provide strong evidence supporting the social model of health by highlighting the key role of social systems and non-clinical interventions in precision public health to improve health outcomes for all. [ABSTRACT FROM AUTHOR]

Men with cystic fibrosis are nearly always infertile due to congenital bilateral absence of the vas deferens, but can undergo assisted reproduction. Ill health may influence reproductive choices. This paper reports data on fertility and family formation in CF including the use of assisted reproduction in a total cohort of 205 men (mean age 30.9, range 16.6–64.3 years) studied over a 10-year period. Overall 102 (49.5%) were single, 52 (25.7%) were married, 48 (23.3%) were in long-term heterosexual relationships, and 3 (1.5%) were in same-sex relationships. One (0.5%) was fertile naturally. In total, 30 children were born to 23 (11%) men by assisted reproduction: 4 used donor sperm and 19 had sperm retrieval and intracytoplasmic sperm injection (ICSI). Two men each adopted two children; 15 (7.3%) men were acting as step-fathers to 20 children from their partners' previous relationships. Overall 41 (20%) men had fatherhood roles. ICSI was unsuccessful in 4 men. A further 16 men were referred for fertility treatment but did not proceed. Of the 19 men having children by ICSI, 3 died leaving 4 children. Men with CF face complex decisions when considering their relationships, fertility and fatherhood. [ABSTRACT FROM AUTHOR]

This paper examines women's experiences with decision-making about non-invasive prenatal testing (NIPT). Such tests offer knowledge about chromosomal disorders early in pregnancy, without the risk of miscarriage associated with invasive procedures such as amniocentesis. Based on qualitative interviews with women in Germany who used, or declined, NIPT, we show how some women, who would not consider amniocentesis due to the risk of miscarriage, welcome the knowledge provided by, and the additional agency resulting from, NIPT. For others, declining the offer to "know more" becomes increasingly difficult to articulate. The absence of risk strips women of a "good reason" to justify their decision not to test, thus implicitly challenging their "right not to know." Moreover, NIPT heightens moral dilemmas within relationships with partners, existing children, and sometimes other close relatives. While clinically "non-invasive," we argue that NIPT changes decision-making in an ethically and socially highly significant way. [ABSTRACT FROM AUTHOR]

To explore the clinical uptake of pharmacogenetic/pharmacogenomic toxicity testing to reduce adverse drug reaction incidences, this paper analyzes data collected through semi-structured face-to-face interviews with clinicians and/or clinician-scientists, primarily in the context of cancer treatment in multi-ethnic California (US), Vancouver (Canada) and Singapore. Recurrent themes in the data include the following: first, the scientific evidence for drug-gene interactions is perceived to be generally weak. Second, the primacy of medical treatment's efficacy over toxicity is the predominant frame through which clinicians consider testing. Third, physicians tailor their decisions according to each patient's tolerance levels for toxicity. Fourth, racially and ethnically based toxicity risk estimates are a factor shaping the clinical uptake of genetic tests, but they are controversial. These factors contribute to the low clinical uptake of toxicity testing for predictive purposes. We argue that the decision-makers' framing and perception are additional features to be considered in Hedgecoe's (2008) "clinical usefulness" framework. [ABSTRACT FROM AUTHOR]

Predictive medicine presents opportunities to consider later life under conditions of illness, such as dementia. This paper examines how family caregivers (N = 27) assess the opportunity of prediction and early diagnosis of dementia for oneself based on their particular experience. Furthermore, it compares their attitudes with laypersons' attitudes (N = 43) towards genetic testing of APOE. By this, we elaborate how much personal experience impacts anticipation and affects, but also moral attitudes towards predictive medicine. Differences in our settings do not allow for direct comparison, so our analysis focuses on multiple similarities in the assessments of predictive (non-genetic vs. genetic) testing. Groups' reasoning showed also differences influenced mainly by personal experience. Family caregivers addressed more responsibility towards family and had more hopes into medical treatments. To cope with the disease, they expressed expectations to start with medicine and care decisions as early as possible. Laypersons, however, stressed self-determination more and expressed worries about the influence of the pharmaceutical industry by referring to unnecessary medication and, implicitly, the medicalization of aging. [ABSTRACT FROM AUTHOR]

Direct-to-consumer genetic testing products and their participatory social media outlets provide users with new ways to understand ancestral identity, build community around shared results, and conceptualize the role of genetic determinism in their lives. In this article, I explore of role of user-generated information constructed with results from direct-to-consumer genetic scanning services such as 23andme, GEDMatch, AncestryDNA, MyHeritage. In particular, this paper considers how social capital is accumulated and disseminated utilizing these participatory tools in the communication practices of users. Through the sharing of genealogical knowledge, historical expertise, communication technology skills, access to genealogical services, selective behaviors such as cooperation, trust building, and a reliable presence on these social networking sites are examined. Thus this article aims to examine consumer contact practices and information sharing of social capital in the form of familial origin narratives, genetic ancestry estimations, and how this communication shapes user interpretation of genetic results. [ABSTRACT FROM AUTHOR]

Preimplantation genetic testing (PGT) is presently the only option available for detecting genetic conditions in embryos created through in vitro fertilization (IVF) prior to implantation. Thus PGT eliminates the dilemma of pregnancy termination following unfavorable prenatal diagnosis test results. Complex chromosome rearrangements (CCRs), although very rarely reported in humans, represent a significant clinical problem for their carriers. CCRs include at least three breakpoints affecting two or more chromosomes. In three-breakpoint translocations, theoretically sixty-four different chromosomal sets are produced. Only two of them will be balanced and will lead to the birth of a phenotypically normal child. Therefore, CCR carriers are at increased risk of chromosomally unbalanced conceptions, resulting in spontaneous abortions or birth of offspring with intellectual disability and/or congenital anomalies. The reproductive options before such families are: natural conception followed by prenatal diagnosis; donor gametes; adoption or PGT. In this paper we discuss the current state of the PGT field and report on two PGT-cases for CCR in families with infertility and recurrent pregnancy losses. The families underwent IVF-PGT on day 3 and day 5 embryos and whole genome microarray analysis. [ABSTRACT FROM AUTHOR]

Identifying the genetic basis of disease is not a straightforward medical procedure but implicates the broader social, cultural and political context. Ethnicity represents an important part of this context, particularly given the confused and poorly informed debate about genetic differences among supposedly different 'racial' populations. Debates about the 'new genetics', however, have not engaged fully with the issue of ethnicity and racism. This paper, by reviewing a mix of empirical and theoretical debates, explores the discursive practices that inform current thinking on genetics, ethnicity and race. The account begins by exploring some of the philosophical tensions inherent in providing genetic testing. In doing so, the paper argues that current debates about genetics are not neutral but evoke a specific set of received ideas and codes of intervention, embodying social and power relationships. The paper then broadens the discussion by exploring the general meaning of screening and counselling for the 'lay' population, before focusing on the process of providing information and identifying people as carriers. The paper concludes by suggesting that the social space in which the 'new genetics' is enacted, understood and given meaning raises generic concerns, irrespective of ethnicity. These include the potential tension between prevention and informed decision making , whereby ideas about empowering individuals to exercise choice exist alongside a more general societal concern with minimising impairment and illness. In more practical terms, individual choice is compromised by poor-quality care, inadequate information, insensitivity to an individual's worries and concerns and a more general failure to meet his or her needs. At the same time, however, the often racialised perspectives articulated through the activities of service professionals can further complicate the choices and decisions available to minority ethnic populations. The failure to recognise and respond to diversity; blaming minority ethnic populations for their health problems; and the pervasiveness of racist myths and stereotypes in service provision, serve to disadvantage minority ethnic populations. This explains why themes such as equity and access, political engagement as well as more general notions of deservingness based on the construction of citizenship and identity emerge as fundamental in making sense of the relationship between ethnicity and the politics of the 'new genetics'. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to study the effect of preimplantation genetic testing for aneuploidies (PGT-A) performed at blastocyst stage on the levels of first trimester biomarkers. Methods: This is an observational, collaborative, retrospective study. Seven hundred and twenty-eight patients were included in the study. Patients were with singleton pregnancies resulting from either natural conception (NC), or assisted reproductive techniques (ARTs) with PGT-A and frozen embryo transfer (FET) (ART/PGT-A/FET) or after ART without PGT-A and fresh ET (ART/no PGT-A/fresh ET) or FET (ART/no PGT-A/FET), who had first trimester combined screening test between 11 and 14 gestational weeks. They were stratified into four groups: group A (ART/PGT-A/FET) – 143 patients; group B (ART/no PGT-A/FET) – 100 patients; group C (ART/no PGT-A/fresh ET) – 346 patients, and group D (NC) – 139 patients. Results: Statistically significant differences among the examined groups were observed for maternal age, BMI, ethnicity, and parity. The median placenta-associated plasma protein (PAPPA) was lowest in the group with ART/PGT-A/FET and the highest result was obtained in the group with ART/no PGT-A/FET. Statistically significant difference in the median PAPP-A levels was identified among the examined groups (p = .0186). When a subgroup analysis was performed, a statistically significant difference was observed in the median PAPP-A between ART/ PGT-A/FET group versus ART/no PGT-A/FET group (p = .01) and NC versus ART/no PGT-A/FET (p = .01). A similar trend toward statistical significance was noted when comparing NC versus ART/no PGT-A/fresh ET (p = .06). Multivariate analysis elucidated that when age is present in the model, the effect of any method of conception or testing for aneuploidy disappears. The other factors (BMI, ethnicity, and parity) do not influence the levels of PAPP-A. The lowest median free human chorionic gonadotropin (b-HCG) was recorded in the NC group and the highest result was identified in the group with IVF/PGT-A/FET. No statistically significant difference was observed in the median concentration levels of free b-hCG among the compared groups (p = .5789) and when subgroup analysis was performed (p>.05). The normality of the distribution of variables was analyzed by the Kolmogorov–Smirnov test and the median PAPP-A and free bhCG concentration difference by the Wilcoxon rank-sum test with nonparametric ANOVA. Conclusions: Testing for aneuploidy (PGT-A) and the decision to transfer either fresh or cryopreserved embryos (ET) appear not to affect the levels of first trimester biochemical markers. The findings of the present study should be a baseline for future studies and could be used to improve the antenatal screening counseling for women with ART pregnancies and PGT-A. [ABSTRACT FROM AUTHOR]

While developments in genetic medicine are widely considered to bring forward pressing policy challenges, the question how genetic diagnostics are integrated into and distributed within existing health-care infrastructures has virtually been ignored. This paper addresses the distribution of genetic diagnostics through the framework of bioconstitutionalism, which suggests that basic categories for the allocation of rights and duties in law and policymaking are redefined together with and through specific scientific and technological ways of understanding and intervening in life. The paper thus analyzes the coproduction of diagnostic and distributive approaches to familial hypercholesterolemia (FH), a hereditary form of high cholesterol, in the Netherlands, the United Kingdom and Germany. It describes how a commitment to a genetically narrow screening program in the Netherlands reflects a commitment to providing care to specific subcommunities of people at risk; how a broad and predominantly phenotypic understanding of FH in the United Kingdom can be understood in terms of an emphasis on comprehensive population coverage and how the framing of high cholesterol as a regular risk factor in Germany expresses a rule-bound notion of justice. The paper thus suggests that particular culturally situated imaginations of distributive justice in the distribution of health-care resources underwrite the formation of diagnostic and distributive arrangements. The paper thereby proposes that bioconstitutionalism can provide a valuable contribution to (comparative) health policy analysis by lying bare how policies affect individual access to medical care. [ABSTRACT FROM PUBLISHER]

Background: Autism self-advocates' views regarding genetic tests for autism are important, but critical questions about their perspectives arise. Methods: We interviewed 11 autism self-advocates, recruited through autism self-advocacy websites, for 1 h each. Results: Interviewees viewed genetic testing and its potential pros and cons through the lens of their own indiviudal perceived challenges, needs and struggles, especially concerning stigma and discrimination, lack of accommodations and misunderstandings from society about autism, their particular needs for services, and being blamed by others and by themselves for autistic traits. Their views of genetic testing tended not to be binary, but rather depended on how the genetic test results would be used. Interviewees perceived pros of genetic testing both in general and with regard to themselves (e.g., by providing "scientific proof" of autism as a diagnosis and possibly increasing availability of services). But they also perceived disadvantages and limitations of testing (e.g., possible eugenic applications). Participants distinguished between what they felt would be best for themselves and for the autistic community as a whole. When asked if they would undergo testing for themselves, if offered, interviewees added several considerations (e.g., undergoing testing because they support science in general). Interviewees were divided whether a genetic diagnosis would or should reduce self-blame, and several were wary of testing unless treatment, prevention or societal attitudes changed. Weighing these competing pros and cons could be difficult. Conclusions: This study, the first to use in-depth qualitative interviews to assess views of autism self-advocates regarding genetic testing, highlights key complexities. Respondents felt that such testing is neither wholly good or bad in itself, but rather may be acceptable depending on how it is used, and should be employed in beneficial, not harmful ways. These findings have important implications for practice, education of multiple stakeholders, research, and policy. [ABSTRACT FROM AUTHOR]

Introduction: Patients with primary immunodeficiency secondary to abnormal recombinase activating genes (RAG) can present with broad clinical phenotypes ranging from early severe infections to autoimmune complications and inflammation. Immunological phenotype may also vary from T−B− severe combined immunodeficiency to combined immunodeficiency or antibody deficiencies with near-normal T and B cell counts and even preserved specific antibody response to pathogens. It is not uncommon that RAG variants of uncertain significance are identified by serendipity during a broad genetic screening process and pathogenic RAG variants are increasingly recognized among all age groups, including adults. Establishing the pathogenicity and clinical relevance of novel RAG variants can be challenging since RAG genes are highly polymorphic. This review paper aims to summarize clinical phenotypes of RAG deficiencies and provide practical guidance for confirming the direct link between specific RAG variants and clinical disease. Lastly, we will review the current understanding of treatment option for patients with varying severity of RAG deficiencies. Area covered: This review discusses the different phenotypes and immunological aspects of RAG deficiencies, the diagnosis dilemma facing clinicians, and an overview of current and advancement in treatments. Expert opinion: A careful analysis of immunological and clinical data and their correlation with genetic findings helps to determine the significance of the genetic polymorphism. Advances in functional assays, as well as anti-cytokine antibodies, make it easier to resolve the diagnostic dilemma. [ABSTRACT FROM AUTHOR]

This paper explores clinicians' and scientists' accounts of genomic research in cancer care and the complexities and challenges involved with delivering this work. Contributing to the sociology of (low) expectations, we draw on sociological studies of uncertainty in medicine to explore their accounts of working with uncertainty as part of the management of patient and institutional expectations. We consider their appeals to the importance of modest inquiry and framing of the uncertainties of genomic medicine as normal and at times welcome as they sought to configure professional autonomy and jurisdictions and cultivate an experimental ethos amongst their patients. We argue that these types of uncertainty work [Star, S. L. 1985. "Scientific Work and Uncertainty." Social Studies of Science 15 (3): 391–427] are a key feature of managing expectations at the intersections of genomic research and clinical care. [ABSTRACT FROM AUTHOR]

Social scientists have found that direct-to-consumer genetic ancestry testing can increase the influence of genetic notions of identity, but has a varying effect on test takers depending on the individual, social and political context. This paper considers the potential effects of genetic ancestry testing on the Indigenous peoples of Australia. We first review the effects of genetic ancestry testing in different populations, particularly Native Americans. We then draw on a comparative analysis of indigenous political structures in the United States and Australia in order to assess the likely impact of genetic ancestry testing in Australia in the coming years. The most salient point of difference is Australia's relatively broader definition of Indigenous status. Due to this difference, genetic ancestry testing is likely to have minimal social impact among those who already identify as Indigenous, but may significantly impact those who discover genetic ancestry and do not yet identify as Indigenous. [ABSTRACT FROM AUTHOR]

Background: Inherited retinal degenerations (IRDs) encompass a wide spectrum of genetic ocular diseases characterized by considerable genetic and clinical heterogeneity. Methods: Complete ophthalmic examination and next-generation sequencing. Results: We describe a patient with no family history of vision loss, who at the age of 28 years developed visual impairment consistent with a severe form of retinitis pigmentosa. Genetic testing by means of whole exome sequencing identified a homozygous variant in the gene IDH3A. To date, only three papers have reported mutations in IDH3A, in families with early-onset retinal degeneration with or without the presence of macular pseudocoloboma. Conclusion: This study highlights the importance of including this rarely-mutated gene in the molecular diagnostic set-ups for IRDs, and further delineates the phenotypic spectrum elicited by mutations in IDH3A. [ABSTRACT FROM AUTHOR]

This paper considers how the globalized discourse of genetic risk in cousin marriage is shaped, informed and taken up in local moral worlds within the context of Qatar. This paper investigates the way Qataris are negotiating the discourse on genetics and risk. It is based on data from ongoing ethnographic research in Qatar and contributes to anthropological knowledge about this understudied country. Participants were ambivalent about genetic risks and often pointed to other theories of causation in relation to illness and disability. The discourse on genetic risk associated with marrying in the family was familiar, but for some participants the benefits of close marriage outweighed potential risks. Furthermore, the introduction of mandatory pre-marital screening gave participants confidence that risks were monitored and minimized. [ABSTRACT FROM AUTHOR]

The article discusses various papers published in this issue including one by Inthorn on the use of the term risk in medicine, one by Howard and Iwarsson on the use of the taxonomy of uncertainty, and one by Falahee et al. on the views of medical personnel on risk from genetic testing.

The starting point of the MindTheRisk project has been to raise socio-political questions about whether lay public’s understanding is satisfied about the genetic information they receive, and to what extent regulators do take this aspect on board when they decide to allow or restrict genetic testing or to develop communications about genetic testing. This article draws on the concepts that have emerged among the risk research community to tackle “risk tolerance’’. It explores the application of those concepts to the sharing and regulating of genetic risk information. We start with a conceptualisation of risk acceptability/tolerability in the genetic context, before turning to concrete hurdles that need to be overcome and questions that need to be answered. Finally, we suggest some direction for policy. The paper is based on an in-depth review supplemented by pilot interviews conducted with the European Medicines Agency, National regulatory agencies, academic and members of a patient organisation, all directly involved in policy. [ABSTRACT FROM PUBLISHER]

Advances in genomic technologies and a growing trend towards stratified and preventive approaches to medicine mean that increasing numbers of individuals may have access to information about their genetic makeup, and their risk of developing diseases. This is likely to impact on healthcare professionals involved in the delivery of genetic tests, or in supporting patients who are affected by a disease with a genetic risk factor. It is therefore important to understand healthcare professionals’ perceptions about providing these services, and how they feel about communicating information about genetic risk to patients. This paper provides a systematic review and metasynthesis of qualitative research exploring healthcare professionals’ perceptions of genetic risk in the context of predictive genetic testing for chronic disease. Healthcare professionals expressed a range of reservations about the utility of predictive testing in this context. Professionals judged patients’ understanding of risk information to be limited and subject to bias and a range of sociocultural influences. Concerns about the psychosocial impact of genetic risk information were frequently cited, both in relation to individual patients and the wider impact on their families and communities. The need for provision of multidisciplinary support was described. The concept of responsibility was also an important theme. Healthcare professionals recognized the responsibility that accompanies risk knowledge, and that ultimately this responsibility lies with the patient, not the provider. Our analysis suggests that professionals’ evaluation of the utility of predictive genetic testing is influenced not only by resource deficits, but may also be interpreted as a response to challenging ethical and social issues associated with genetic risk, that are not well aligned with current medical practice. [ABSTRACT FROM PUBLISHER]

New technologies have afforded increased access to genetic testing providing valuable information for individuals and those biologically related. However, the management of such information is challenging for psychologists given the ethical issues that may arise. This paper aims to review the utility of existing ethical standards and current legislation for psychologists when encountering genetic information. Current legislation and guidelines involved in the management of genetic information applicable for psychologists is critically reviewed in light of relevant ethical principles. While knowledge of information that has arisen from genetic testing may guide psychological therapy, intervention, and education, psychologists have a responsibility to uphold their ethical obligations in order to meet the needs of their clients and their families and to prevent harm. Outside the domain of ethically approved human research, and specific guidance for trained genetic counsellors in Australia, ethical guidance on the management of human genetic information is not readily available for psychologists. Technological advances can be expected to continue to present epistemic dilemmas about the use of genetic material. The implications for future psychological practice is discussed. : What is already known about this topic: (1) Increased access to genetic testing can provide valuable information for individuals and those biologically related. (2) Genetic testing poses new and significant challenges for psychologists, especially in respect to the ethical issues that can occur. (3) Given that findings from genetic testing may guide therapy goals, interventions, and psychoeducation, psychologists have a responsibility to uphold ethical obligations in order to meet the needs of their clients and their families and to prevent harm. Yet, clear guidelines for ethical obligations regarding the handling of genetic testing are not readily available. What this topic adds: (1) Within the framework of current legislation, the four core ethical standards of beneficence, autonomy, justice, and non-maleficence work together with the APS Code of Ethics and ethical guidelines for psychologists. (2) While the use of genetic information has the potential to affect whole communities, it should be used in such a way that maintains ethical principles, meeting the needs of the individual and family. (3) It is important that ethical guidelines for genetic information in the field of psychology remain cohesive to meet the needs of rapid technological advances and changing legislation. [ABSTRACT FROM AUTHOR]

Genetic and genomic data are increasingly guiding clinical care for cancer patients. To meet the growing demand for precision medicine, patient-facing oncology staff will be a part of leading the provision of genomic testing. A scoping review was undertaken to identify the range of genetic and genomic learning needs of oncologists and oncology nurses. Learning needs were reported relating to interpretation of genomic data, clinical decision-making, patient communication and counseling, and fundamentals of genetics and genomics. There was a lack of empirical research specific to oncology nurses and their learning needs in tumor sequencing. Our findings suggest that oncologists and oncology nurses need tailored support, education and training to improve their confidence and skills in adopting genomic testing into clinical practice. [ABSTRACT FROM AUTHOR]

APC-associated polyposis is a rare hereditary disorder characterized by the development of multiple adenomas in the digestive tract. Individuals with APC-associated polyposis need to be managed by specialized multidisciplinary teams in dedicated centers. The study aimed to review the literature on Familial adenomatous polyposis (FAP) to provide an update on diagnostic and surgical management while focusing on strategies to minimize the risk of desmoid-type fibromatosis, cancer in anorectal remnant, and postoperative complications. FAP individuals require a comprehensive approach that includes diagnosis, surveillance, preventive surgery, and addressing specific extracolonic concerns such as duodenal and desmoid tumors. Management should be personalized considering all factors: genotype, phenotype, and personal needs. Total colectomy and ileo-rectal anastomosis have been shown to yield superior QoL results when compared to Restorative Procto colectomy and ileopouch-anal anastomosis with acceptable oncological risk of developing cancer in the rectal stump if patients rigorously adhere to lifelong endoscopic surveillance. Additionally, a low-inflammatory diet may prevent adenomas and cancer by modulating systemic and tissue inflammatory indices. FAP management requires a multidisciplinary and personalized approach. Integrating genetic advances, innovative surveillance techniques, and emerging therapeutic modalities will contribute to improving outcomes and quality of life for FAP individuals. [ABSTRACT FROM AUTHOR]

Genetic testing can help individuals and families by giving them a sense of control over their futures; however, results of some types of testing cause individuals and their families great distress and anxiety. The purpose of this paper is to report findings from a systematic review of literature about perceived benefits and harms associated with genetic testing. A second purpose was to determine if perceived benefits and harms varied by age and gender. We reviewed a sample of 30 articles published between 1997 and 2009. Most of the articles were other literature reviews. We summarized the benefits and harms associated with each type of genetic testing and made recommendations for future study. As technologies increase, genetic testing will expand and psychiatric mental health nurses must be prepared to meet the challenges of psychosocial disorders that may develop in response to genetic testing. [ABSTRACT FROM AUTHOR]

This paper uses the concept of ‘ethicality’ to analyse focus-group conversations in New Zealand on biobanking and genetic testing. ‘Ethicality’ has been used by Arohia Durie, a Maori educationist, to highlight how ethical talk and practice is historically and socially positioned, situated within specific life-worlds, embedded within always partial communities, and articulated within individual life narratives. This situated ethicality is identified in the talk of Maori and non-Maori research participants. The authors (a moral philosopher, two sociologists and a kaupapa Maori social researcher) argue that serious consideration of ethicality presents significant challenges to the abstracted character of much expert ethical analysis, while also illustrating connections between ‘ethics talk’ and expert discourses. [ABSTRACT FROM AUTHOR]

In February 2015, 23andMe received clearance from the United States Food and Drug Administration (FDA) for a carrier status test for a gene linked to Bloom syndrome. This was the first FDA authorization to market a direct-to-consumer (DTC) genetic test. Then, in April 2017, 23andMe obtained marketing clearance for an additional 10 tests that communicate information about individual disease risk. For roughly a decade it had been unclear whether FDA would regulate health-related DTC genetic tests. The recent approvals now provide an opportunity to examine how the Agency, in practice, has exercised its regulatory authority. This paper is the first case study to examine in detail how FDA has set standards for the marketing approval of DTC genetic tests. [ABSTRACT FROM PUBLISHER]

Introduction: Congenital heart disease (CHD) is the most common birth defect in humans. In spite of tremendous advance in medical care, CHD is still a major contributor to substantial morbidity and mortality. Aggregating evidence demonstrates that genetic defects play a pivotal role in the pathogenesis of CHD, and an increasing number of genetic mutations have been identified to be responsible for CHD. Areas covered: This paper is restricted to the molecular diagnosis of CHD, and highlights loss-of-function mutations in the genes associated with CHD. The newly-made progress in the molecular genetics of CHD is reviewed in this article. Expert commentary: Heart development is a precisely-coordinated biological process, involving in cellular proliferation, differentiation, migration, and integrated morphogenetic interactions, and interruption of this process predominantly by genetic risk factors leads to CHD. To date, mutations in over 60 genes have been causally linked to CHD, of which most mutations cause a loss-of-function effect. Using next generation sequencing technology and data processing software, new CHD-associated genes will be more easily discovered. Identification of the CHD-causative genes is of significant importance in genetic diagnosis, early prophylaxis and personalized treatment of CHD patients. [ABSTRACT FROM PUBLISHER]

Whole-exome sequencing (WES) has been instrumental in the discovery of novel genes and mechanisms causing Mendelian diseases. While this technology is now being successfully applied in a number of clinics, particularly to diagnose patients with rare diseases, it also raises a number of ethical, legal and social issues. In order to identify what challenges were directly foreseen by technology users, we performed a systematic review of the literature. In this paper, we focus on recent publications related to the use of WES in the pediatric context and analyze the most prominent challenges raised by technology users. This is particularly relevant considering that a) most patients currently undergoing testing using WES to identify the genetic basis for rare diseases are children and b) their lack of capacity to consent for themselves makes them a vulnerable population and generates the need for specific ethical, legal and regulatory procedures. We identified key challenges that related to four main categories: (1) intake; (2) sequence production and analysis; (3) reporting of results and counseling considerations and (4) collaborative data interpretation and data sharing. We then contextualize these challenges in light of the recent recommendations and guidelines, published by professional societies that have significant potential to impact the field. [ABSTRACT FROM AUTHOR]

Medical science has enabled the creation of families through the use of donor conception but some lifelong policy and practice implications are only recently being recognized. Research and practice have shown that donor conception can, for some, carry substantial long-term consequences. In this paper we present findings from a questionnaire-based study that sought to shed light on donor-conceived adults’ and gamete donors’ views on service and support needs when searching for genetic relatives with the aid of DNA testing. The findings demonstrate the complexity and sensitivity of providing services in this newly emerging area of need. Such provision requires collaboration between very different disciplines and agencies (scientific and psychosocial), introduces the potential for blurring of lines of accountability and responsibility, and highlights the challenges of identifying appropriate funding streams. In addition, the findings demonstrate the opportunities and limitations afforded by the use of DNA in identifying unknown genetic relatives. [ABSTRACT FROM PUBLISHER]

A genetic predisposition seems to be involved in biliary tract cancer, but the prevalence of germline mutations in BTC remains unclear, and the therapeutic role of the germline pathologic variants is still unknown. The aim of the present work is to systematically review the data available on the hereditary predisposition of biliary tract cancer by a specific research on PubMed, in order to highlight the most important critical points and to define the current possible role of germinal testing and genetic counseling in this setting of patients. Basing on data already available, we decided to start in our institution a specific genetic protocol focused on biliary tract cancer patients, which includes genetic counseling and, if indicated, germline test. The inclusion criteria are: 1) Patient with personal history of oncologic disease other than BTC, 2) Patient with familiar history of oncologic disease (considering relatives of first and second grade), 3) Patient with ≤ 50 years old, 4) Patient presenting a somatic mutation in genes involved in DNA damage repair pathways and mismatch repair. The aim of the presented protocol is to identify germline pathogenic variants with prophylactic and therapeutic impact, and to collect and integrate a significant amount of clinical, familial, somatic, and genetic data. [ABSTRACT FROM AUTHOR]

Aim: To understand awareness, knowledge and preferences regarding genetic testing among the USA general public. Methods: A cross-sectional online survey using a Qualtrics Panel. Results: Among 1600 respondents, 545 (34%) were White, 411 (26%) Black, 412 (26%) Hispanic or Latin(x) and 232 (15%) Asian. Most had heard of ancestry testing (87%) and genetic health risk testing (69%), but a third thought inherited genes were only a little or not at all responsible for obesity (36%) and mental health (33%). The majority preferred pre-emptive pharmacogenetic testing (n = 74%) compared with reactive testing. Statistically significant differences between racial/ethnic groups and rural-urban respondents were observed. Conclusion: Most preferred pre-emptive pharmacogenetic testing; however, about one-quarter preferred reactive testing. Preferences should be discussed during patient–clinician interactions. Plain language summaryWhat is this study about? This study presents a large online survey among the USA general public to understand their awareness, knowledge and preferences about genetic testing and how this may vary by racial/ethnic group and rural/urban status. What were the results? Most survey respondents had heard of ancestry testing (87%) and genetic health risk testing (69%). However, over a third of respondents thought that inherited genes may be only a little or not at all responsible for obesity (36%) and mental health (33%). When asked about preferences for pre-emptive compared with reactive pharmacogenetic testing, the majority preferred pre-emptive testing (n = 74%). Statistically significant differences between racial/ethnic groups as well as rural-urban respondents were seen. What do the results mean? The US general public may have a different understanding of genetic testing for different diseases, and have different preferences when it comes to the timing of testing. Appropriate educational content targeting the link between genetics and specific diseases should be prepared, and preferences for pre-emptive or reactive testing should be discussed during visits with healthcare providers. Summary points Genetic information is rapidly evolving and previous studies rarely focused on the extent of familiarity with newer genomic terms and procedures among the USA general public. One of the striking findings from this survey is that half of the total respondents were not aware of genetic testing in the context of choice of treatments, identifying adverse events from medications, and medication dosage optimization. A relatively smaller proportion of Black respondents and rural residents thought that genetic tests could identify medication side effects or optimize dosages compared with their counterparts. Most respondents were willing to choose pre-emptive over reactive testing to select the best medications for them. [ABSTRACT FROM AUTHOR]

Background: The ability to obtain genetic information can now be accomplished in far greater detail, and more quickly than in the past. It is important to understand obstetrician-gynecologists' (ob-gyns) screening practices as these changes occur.Methods: Cross-sectional survey was performed by mailing paper surveys to Fellows of the American College of Obstetricians and Gynecologists and a subset of Fellows who belong to the Collaborative Ambulatory Research Network (CARN).Results: Response rates were 57% for the CARN network. Almost all responders (92%) offer population-based genetic screening in the prenatal period and almost all (93%) conduct counseling prior to the provision of genetic testing. Almost all (92%) counsel patients when the result is positive, with 46% being the primary counselor and 55% calling the patient themselves. When results are negative, 73% counsel with 58% indicating they are the primary counselor and 17% call patients themselves. A total of 72% have received continuing medical education (CME) on genetics within 5 years, with 79% receiving CME at conferences and 21% receiving CME online.Conclusion: Ob-gyns have a large role in providing patients new genetic screening technologies. This role requires a significant knowledge base, some of which can be obtained by online modules; however, our study suggests online education is underutilized as a means for CME on genetic screening among ob-gyns. [ABSTRACT FROM AUTHOR]

A significant number of multiple pregnancies and births worldwide continue to occur following treatment with Assisted Reproductive Technologies (ARTs). Whilst efforts have been made to increase the proportion of elective single embryo transfer (eSET) cycles, the multiple pregnancy rate or MPR remains at a level that most consider unacceptable given the associated clinical risks to mothers and babies, and the additional costs associated with neonatal care of premature and low birth weight babies. Northern Europe, Australia and Japan have continued to lead the way in the adoption of eSET. Randomised controlled trials or RCTs, meta-analyses and economic analyses support the implementation of an eSET policy, particularly in light of recent advances in ARTs. This paper provides a review of current evidence and an update to the eSET guidelines first published by Cutting et al. (2008) intended to assist ART clinics in the implementation of an effective eSET policy. [ABSTRACT FROM AUTHOR]

Direct to consumer (DTC) genetic testing has given rise to much controversy, especially in relation to testing for health diagnostic purposes. This paper will consider whether consumers' use of DTC genetic testing should be understood as predominantly recreational. It will be argued that recreational testing can encompass all information domains, including most kinds of predictive health risk information. In relation to recreational testing the potential identity implications for the consumer become a significant concern, more so than the risks more traditionally associated with genetic testing. It will be concluded that while the DTC genetic testing sector is beset by numerous problems and an increase in consumers' genetic literacy is highly desirable, consumers' engagement with DTC genetic testing may be less problematic than sometimes assumed. [ABSTRACT FROM AUTHOR]

The prevalence of celiac disease (CD) is increasing. Despite an increased awareness and an improvement in diagnostic testing, the majority of individuals with CD remain undiagnosed. Currently, genetic testing in screening for CD is used only to exclude a diagnosis or reinforce a strong clinical suspicion. In this paper, we review the most current literature regarding genetic testing in CD. In response to important data revealing that an individual's HLA haplotype is one of the strongest known predictors of CD, we propose genetic screening for at-risk infants to stratify individuals based on genetic risk to ultimately create genetic specific screening algorithms. [ABSTRACT FROM AUTHOR]

Accurate diagnosis of macular atrophy is paramount to enable appropriate treatment when novel treatments for geographic atrophy and macular dystrophies become available. Genetic testing is useful in distinguishing between the two conditions but is not feasible for the majority of patients in real-world clinical practice. Therefore, we aimed to investigate the potential misdiagnosis of inherited macular dystrophy as age-related macular degeneration (AMD) in real-world ophthalmic practice to assist in the development of guidelines to improve diagnostic accuracy while minimizing genetic testing for targeted patients. Retrospective review of the medical records of patients diagnosed with AMD, which included imaging, between 1995 and 2023 from a large multidisciplinary private ophthalmic practice in Australia. We will use a stepwise method to screen for probable cases of macular dystrophy, followed by a consensus review by an expert panel. The outcomes are (1) to determine the potential misdiagnosis rate of macular dystrophy as atrophic AMD by retinal specialists and general ophthalmologists; (2) to identify clinical imaging modalities that are most useful for differentiating macular dystrophy from atrophic AMD; and (3) to establish preliminary guidance for clinicians to improve the diagnosis of macular atrophy from AMD in practice, and thereby target cost-efficient genetic testing. Improving the diagnostic accuracy of both AMD and macular dystrophy, while ensuring cost-efficient genetic testing, will improve the targeted treatment of macular diseases when emerging treatments become available. [ABSTRACT FROM AUTHOR]

Objective: Given the psychosocial and ethical burden, patients with hypertrophic cardiomyopathy (HCMs) could benefit from the establishment of genetic probability prior to the test. This study aimed to develop a simple tool to provide genotype prediction for HCMs. Methods: A convolutional neural network (CNN) was built with the 12-lead electrocardiogram (ECG) of 124 HCMs who underwent genetic testing (GT), externally tested by predicting the genotype on another HCMs cohort (n = 54), and compared with the conventional methods (the Mayo and Toronto score). Using a third cohort of HCMs (n = 76), the role of the network in risk stratification was explored by calculating the sudden cardiac death (SCD) risk scorers (HCM risk-SCD) across the predicted genotypes. Score-CAM was employed to provide a visual explanation of the network. Results: Overall, 80 of 178 HCMs (45%) were genotype-positive. Using the 12-lead ECG as input, the network showed an area under the curve (AUC) of 0.89 (95% CI, 0.83–0.96) on the test set, outperforming the Mayo score (0.69 [95% CI, 0.65–0.78], p < 0.001) and the Toronto score (0.69 [95% CI, 0.64–0.75], p < 0.001). The network classified the third cohort into two groups (predicted genotype-negative vs. predicted genotype-positive). Compared with the former, patients predicted genotype-positive had a significantly higher HCM risk-SCD (0.04 ± 0.03 vs. 0.03 ± 0.02, p <0.01). Visualization indicated that the prediction was heavily influenced by the limb lead. Conclusions: The network demonstrated a promising ability in genotype prediction and risk assessment in HCM. Patients with genotype-positive hypertrophic cardiomyopathy (HCM) have a higher risk of severe heart failure and sudden cardiac death (SCD). A deep learning-derived 12-lead electrocardiogram was developed, outperformed the conventional methods in genotype prediction, and showed a promising future in SCD risk assessment in HCM. [ABSTRACT FROM AUTHOR]

Objectives. Hereditary transthyretin amyloidosis caused by the (ATTRv) p. Val142Ile variant is a common cause of cardiac amyloidosis among Western African countries and Afro-Americans populations. However, in recent years, Caucasian patients have been identified in greater numbers, raising the question of whether this variant has been undeappreciated in this population. We now have new cases of cardiac amyloidosis caused by the p.Val142Ile from a center in northern Portugal. In addition, we reviewed and discussed the published data concerning p.Val142Ile in Caucasians. Design. Patients diagnosed with cardiac amyloidosis underwent genetic testing using TTR gene sequencing and their relatives were recommended for genetic counsellingand testing if a pathogenic TTR variant was found. In our center, we reviewed the clinical data of patients who had the p.Val142Ile variant. A review of published cases of p.Val142Ile in Caucasians was also performed, to which our data was compared. Results. We found three ATTRv patients with the p.Val142Ile variant (one homozygotic), all Caucasian males with a median age at diagnosis of 69 years old. All of them had heart failure and arrhythmias. During the follow-up period, two patients died. There were 47 unrelated unrelated Caucasian cases of ATTRv p.Val142Ile variant reported worldwide until May 2022. Conclusions. Our findings add to the mounting evidence that the global prevalence of p.Val142Ile is likely understated. This highlights the importance of the systematic screening of the TTR gene in amyloidosis and phenocopies, as well as larger epidemiologic studies to determine the true ATTRv p.Val142Ile prevalence in non-African communities. [ABSTRACT FROM AUTHOR]

Thalassaemia is the commonest monogenic disease in Sri Lanka, affecting over 3500 children and half-a-million thalassaemia carriers. This is a review of 82 amniocenteses performed from 2006 to 2016, in the largest prenatal diagnoses study for thalassaemia carried out in Sri Lanka. Amniocenteses were performed between 11 and 12 weeks of ultrasonically confirmed gestation, on mothers with previous thalassaemia major children pregnant for the second time and nulliparous thalassaemia trait women married to trait partners. The Consultant Radiologist, using local analgesia, under ultrasound cover, performed these as an outpatient procedure, at the Teaching Hospital Kandy & Suwasevana Hospital Kandy. The amniotic fluid was analysed by the team of Senior Geneticists, at the Genetech Molecular Diagnostics and School of Gene Technology, Colombo, via the polymerase-chain-reaction based ARMS (Amplification Refractory Mutation Systems) assay. The genetic results indicated the presence of 21% thalassaemia major foetuses, 53% thalassaemia traits and 26% foetuses without thalassaemia mutations. The predominance of the IVS1-5(G-C) mutation in the Sri Lankan population is exemplified, with a low prevalence of HbE thalassaemia. Impact statement Thalassaemia is the commonest monogenic disease in Sri Lanka affecting over 3500 children and half-a-million thalassaemia carriers. Although pre-natal diagnosis by amniocentesis was practised universally for many years, this could not be performed in Sri Lanka as genetic diagnostic facilities were not available until 2005. Therefore, parents with a thalassaemia major child limited their families to one child, by choice or by termination. The results of this study point to a 21% probability of thalassaemia major in the next child, giving the parents a guarded optimism to conceive another child without thalassaemia disease. With siblings being the highest HLA compatibility for Bone Marrow Transplant, that is now being established in Sri Lanka as a permanent cure for thalassaemia, this will bring a ray of hope for these desperate parents to finally cure their previous sick child. Although, 95% of the Sri Lankan mutated genetic sites for thalassaemia are known, more research will be needed to identify the other rare sites. The publication of this paper, with its novelty for pre-natal diagnosis, would encourage clinicians to practice it in other centres and to extend it to families with other genetic disorders. [ABSTRACT FROM AUTHOR]

The article discusses the importance of having the right to one's genetic family history (GFH) with reference to the article "Does Lack of 'Genetic-Relative Family Health History' Represent a Potentially Avoidable Health Disparity for Adoptees" by Thomas May and colleagues in the same issue. Topics covered include the concept of human rights based on the 2008 paper titled "On Human Rights," the importance of GFH in planning one's life pursuits, and the lack of GFH as a human right violation.