European Journal of Human Genetics

ObjectivePatient care using genetics presents complex challenges. Clinical decision support (CDS) tools are a potential solution because they provide patient-specific risk assessments and/or recommendations at the point of care. This systematic review evaluated literature on CDS systems which have been implemented to support genetically guided precision medicine (GPM). Materials and MethodsA comprehensive search was conducted in MEDLINE and Embase, encompassing Jan 1st, 2011 to March 14th, 2023...

Polygenic risk scores (PRS) provide an estimate of the genetic contribution to health conditions. Despite increasing clinical translation, healthcare providers (HPs) report a lack of PRS knowledge, representing a major barrier to safe and effective use in practice. This study aimed to i) identify HPs learning and resource needs for PRS delivery, and ii) outline strategies to best engage clinicians in PRS education, with findings used to inform the co-design of an educational program. To ensure i...

IntroductionPontocerebellar hypoplasia type 2A (PCH2A) is a rare, autosomal recessive disease, caused by a homozygous pathogenic variant in the gene TSEN54 (c.919G>A, p.A307S). Apart from the characteristic pontocerebellar hypoplasia in MRI, PCH2A is clinically characterized by a dyskinetic movement disorder, severe neurodevelopment delay, progressive microcephaly, and, less well recognized, failure to thrive. Additional symptoms such as seizures, gastrointestinal or respiratory problems are com...

BackgroundPatients are increasingly obtaining genetic health information and integrating it into their care with the help of their primary care provider (PCP). However, PCPs may not be adequately prepared to effectively utilize genetic results . Across the VA health system, the Million Veteran Program-Return of Actionable Results-Familial Hypercholesterolemia (MVP-ROAR) study clinically confirms and returns genetic results associated with familial hypercholesterolemia (FH), identified in a natio...

Clinical genetic testing demand has increased in the era of precision medicine. However, availability of cancer genetic services remains limited in the US, prompting a rise in telehealth delivery. This report describes the Penn Telegenetics Program experience using a local healthcare provider collaborative model. From 2018-2025, 473 providers (89.4%) successfully registered. Providers were predominately MD/DO licensed (85.0%). Family medicine was the most frequent speciality (54.3%), followed by...

Despite rapid technological progress being made in genomics, a growing disparity is emerging between healthcare in developed and developing countries. This genomic divide can be partly explained by the scarcity of available genomics workforce and in some parts by limited genomic literacy of healthcare professionals that reportedly deters them from proposing genomic testing in a clinical setting. This study aims to study this gap in a local context and learn how we can reduce this genomic divide ...

There is little country-specific data about how the general public views gene editing therapies. In Autumn 2023 we randomly surveyed the Swiss public, using the Federal Register and stratifying by language region (German, French, Italian), gender and age. We present a representative sample of 3855 responses, including >4000 open-ended comments. When presented with 7 therapeutic options for somatic gene editing, 7% disagreed with all therapeutic options, and 35% supported them all. Most agreed wi...

Current guidelines recommend BRCA1 and BRCA2 genetic testing for individuals with a personal or family history of certain cancers. Three BRCA1/2 founder variants -- 185delAG (c.68_69delAG), 5382insC (c.5266dupC), and 6174delT (c.5946delT) -- are common in the Ashkenazi Jewish population. We characterized a cohort of more than 2,800 research participants in the 23andMe database who carry one or more of the three Ashkenazi Jewish founder variants, evaluating two characteristics that are typically ...

BackgroundEven with the introduction of new genetic techniques that enable accurate genomic characterization, knowledge about the phenotypic spectrum of rare chromosomal disorders is still limited, both in literature and existing databases. Yet this clinical information is of utmost importance for health professionals and the parents of children with rare diseases. Since existing databases are often hampered by the limited time and willingness of health professionals to input new data, we collec...

Digital interventions are potentially promising to improve accessibility and efficiency of genetic counselling services. However, current literature on stakeholder perspectives towards digital tools for cascade testing is limited. Therefore, this focus group study aimed to gain insights into the attitude and perspectives of probands, at-risk relatives (ARR), and genetic healthcare professionals (HCP) towards digital innovations for assistance with both pre-test and post-test counselling and casc...

PurposeThe increasing popularity of direct-to-consumer genetic testing (DTCGT) is thought to be creating a burden on clinical genetic health services worldwide. However, no studies have collected recent evidence regarding the extent of this impact in Australia. MethodsWe administered an online survey to Australian clinical genetics services, asking questions related to DTCGT-related referrals received and outcomes over the past 10 years. ResultsEleven publicly-funded clinical genetics services...

IntroductionGenetic screenings can have a large impact on enabling personalized preventative care. However, this can be limited by the primary use of medical history-based screenings in determining care. The purpose of this study was to understand the impact of DNA10K, a population-based genetic screening program mediated by primary care physicians (PCPs) within an integrated health system to emphasize its contribution to preventative healthcare. MethodsConstruction of the patient experience as...

BackgroundDigital solutions are needed to support rapid increases in the application of genetic and genomic tests (GT) in diverse clinical settings and patient populations. We developed GUIA, a bi-lingual web-based platform that facilitates disclosure of GT results. The NYCKidSeq randomized controlled trial evaluated GUIAs impact on understanding of GT results. MethodsNYCKidSeq enrolled diverse children with neurologic, cardiac, and immunologic conditions who underwent GT. Families were randomi...

Genomic advancements have led to increased utilization of genetic testing in clinical care, yet barriers to accessing genetic counseling and genomics services remain, particularly in the Middle East where inherited diseases are highly prevalent due to consanguinity. Limited knowledge of healthcare professionals experiences in genetic counseling in the Middle East necessitates understanding their perspectives for better service improvement in the region. A survey of 32 healthcare professionals p...

Electronic consultation (e-Consult) programs serve as a conduit between healthcare providers and specialized genetic experts. This retrospective chart review and summary report presents the experience of implementing a Genetics e-Consult Service at the University of California San Francisco (UCSF) from 2016 through 2024 across multiple disciplines. The study examines 622 requests managed by the Genetics team, resulting in the completion of 360 e-Consults (57.8%) and the decline of 262 e-Consults...

The prevalence of comorbidities in individuals with neurodevelopmental disorders (NDD) is not well understood, while these are important for accurate diagnosis and prognosis in routine care and for characterizing the clinical spectrum of NDD syndromes. Therefore, we developed PhenomAD-NDD: an aggregated database with comorbid phenotypic data of 51,227 individuals with NDD, all harmonized into Human Phenotype Ontology (HPO), with in total 3,054 unique HPO terms. We demonstrate that almost all con...

Changes in genetics and genomics sequencing in recent years have created increased demand for genetics professionals, including clinical geneticists and genetic counselors. A significant workforce shortage of these professionals has become widely recognized. This shortage is driven by several factors, including the increased role of genetics in healthcare due to precision medicine initiatives and demand outside of medical practices in clinical and direct-to-consumer genetic testing companies tha...

BackgroundA genetic neurodevelopmental diagnosis (GND) impacts all aspects of a child and familys life. GNDs are rare; most have limited natural history data. We aimed to understand parents experiences around data acquisition about their childs GNDs which can help inform clinical practice. Design and participantsThis analysis is part of the UK multicentre GenROC study. We conducted 17 semi-structured interviews with parents of children with GNDs (aged 0-15 years). Data were analysed following t...

BackgroundNewborn screening (NBS) has progressively expanded through technological innovations, from tandem mass spectrometry enabling expanded NBS (eNBS) to the prospect of genomic NBS (gNBS). While these developments promise earlier diagnosis and richer information, they also raise concerns regarding actionability, uncertainty, equity and psychosocial impact. As technological feasibility alone does not ensure public confidence, parental perspectives are central to evaluating future expansions....

PurposeArtificial intelligence (AI) applications for clinical genetics hold the potential to improve patient care through supporting diagnostics and management as well as automating administrative tasks, thus enhancing and potentially enabling clinician/patient interactions. While the introduction of AI into clinical genetics is increasing, there remain unclear questions about risks and benefits, and the readiness of the workforce. MethodsTo assess the current clinical genetics workforces use, ...