Genome-wide screening can be offered at various stages of life and serve multiple purposes, including early detection of treatable conditions, achieving health benefits, or enhancing reproductive choices. Although genome-wide screening offers many new possibilities, determining which genomic data to analyse, how to interpret results, and how to communicate findings, presents...
Genomic science is a central feature of the UK government’s current 10-year health plan for England, which places significant emphasis on prediction and prevention. Although NHS prevention strategies have long been aimed at catching diseases earlier and at a more treatable stage, genomics until now has focussed largely on diagnosis and treatment. At present, there is limited...
Many people will have had no formal education on health-related genomic testing, so information from media sources may constitute a major influence in shaping ideas and expectations around genomic tests. We undertook a framing analysis of 186 UK news items discussing health-related genomic testing in the context of various recent UK-based initiatives: the 100,000 Genomes Project...
Rare disease studies often rely on small, selected cohorts, are resource-intensive and difficult to scale. UK primary care electronic health record (EHR) databases provide population-based, longitudinal data, but their use for rare genetic disease research has not been systematically examined. Through systematic mapping of publications from five UK primary care EHR databases...
Newborn bloodspot screening (NBS) programs aim to identify babies at risk of developing serious conditions where an effective preventive or ameliorative intervention is available in infancy or early childhood. In recent decades, new testing technologies have been introduced into NBS to expand the number of screened conditions. This now also includes the possible introduction of...
Robust evidence is required to support decision-making about incorporating genomics into healthcare; patient perspectives are crucial. Prior studies centre on people giving research consent for testing, yet significant differences between research and clinical cohorts are well established. We investigated 1690 patients offered genomic testing during clinical care by a range of...
A renewed focus on disease prevention has placed genomics firmly in the spotlight. Policymakers and health services across Europe are considering ways to facilitate disease prevention and early disease detection through population-level initiatives such as newborn genomic screening and polygenic risk scores. This commentary explores, through the lens of duty-based ethics, the...
Despite considerable efforts investigating the genetic aetiology of rare diseases in the past decades, approximately 50% of cases remain without a genetic diagnosis. Many missing diagnoses can be attributed to the limitations of short-read sequencing (SRS), compounded by (mis)-alignment to incomplete and inaccurate reference genomes such as GRCh37/38. SRS cannot resolve many...
Peutz-Jeghers syndrome (PJS) is a very rare autosomal dominant disorder associated with an increased risk of gastrointestinal and gynecological cancers. However, risk estimates vary widely, due to the small size and retrospective nature of most studies, which may introduce recruitment bias. Accurate data are needed to improve cancer screening. The aim of this study was to...
RAC1 is a signal transducer essential for neurodevelopment. Missense variants in RAC1 cause heterogeneous neurodevelopmental disorders whose features include intellectual disability and developmental delay. Individuals with RAC1 variants are categorized by head circumference into microcephalic, normocephalic and macrocephalic groups. We previously described a cohort of...
The integration of genomic sequencing into newborn screening (genomic newborn screening; gNBS) has the potential to identify more presymptomatic babies who could benefit from early intervention compared to traditional universal newborn screening (NBS). Realizing these benefits requires careful navigation of ethical, legal, and social implications (ELSI) to minimize harms, promote...
The integration of genomic sequencing into public health newborn screening (NBS), gNBS, could identify far more children that would meet screening guidelines than existing biochemical NBS. The retention of genomic data from gNBS could have huge benefits for research and could also enable potential clinical reuse. Many different ethical frameworks can support not seeking parental...
Genetics in medicine is rapidly becoming integral to European healthcare, yet access to high-quality genetic counseling remains inconsistent. Genetic counseling empowers patients to make informed decisions about genetic testing, improves clinical management, and mitigates psychosocial harm. Despite growing demand, the genetic counselor profession lacks legal recognition...
This cross-sectional online survey study explores the landscape of medical training on genetic therapies, assessing the experience, expectations and attitudes of medical geneticists, other specialists, and medical trainees in Canada and USA. Among the 315 participants, only 17% reported being “very familiar” with genetic therapies, and 70% expressed dissatisfaction with current...
The classification of congenital malformations has been transformed over recent decades by advances in genetic analysis, so that the natural history of many disorders during childhood is well described. However, implications for adult prognosis and survival are often poorly documented. In Apert syndrome, caused by heterozygous germline mutations in the fibroblast growth factor...
Cystine stones are caused by pathogenic variants in SLC3A1 or SLC7A9. Our prior study revealed a large gap between genetic and clinical prevalence. With increasing discovery of novel variants, we aim to assess how these impact genetic prevalence estimates. Due to the disease rarity, direct patient recruitment and observation is impractical. We applied a population genetics...
With the advent of novel gene therapies, rare genetic diseases once lacking treatments are now being considered for newborn screening programmes (NBS). Wilson and Jungner criteria (drawn on worldwide to guide screening programme evaluation) necessitate effective interventions for a recommendation of screening. Spinal muscular atrophy (SMA) is an example of a condition for which...
Reproductive genetic carrier screening (RGCS) provides people with information about the likelihood of having children with serious inherited genetic conditions. The perspectives of people who have experience with a genetic condition are important in understanding the acceptability of RGCS. Through the Australian Reproductive Genetic Carrier Screening Project (Mackenzie’s Mission...
This paper continues our development of methods for discovery of genetic modifiers of the Duchenne muscular dystrophy (DMD) phenotype. DMD is an X-linked recessive disorder involving progressive muscle tissue loss with replacement by fat and fibrotic tissue, leading in most cases to loss of ambulation (LOA) by early to mid-adolescence. The standard pharmacologic treatment is...
Mitochondrial disorders (MDs) are a diverse group of genetic conditions primarily affecting the oxidative phosphorylation (OXPHOS) system and cellular energy production. Among MDs, Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA), or Microphthalmia with Linear Skin Lesions (MLS) syndrome, is a rare X-linked dominant male-lethal disorder characterized by ocular...