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Background Powerful new genomic technologies are transforming the way healthcare is delivered, shaping medical practice across all specialties. In this rapidly changing landscape, there is an urgent need to equip the clinical workforce with knowledge and skills to navigate the new healthcare terrain. Co-design of healthcare resources with end users is increasingly gaining traction as a method of ensuring that educational content and delivery are tailored to users’ needs, increasing likelihood of use and resulting in better outcomes for patients. Here we describe the co-design and ongoing co-creation of GeNotes – an NHS England National Genomics Education flagship online resource providing genomics education at the point of patient care. Methods To understand the barriers to implementation of genomic medicine and the training needs of the diverse NHS workforce, we adopted a co-design approach with clinicians from both primary and secondary care who are uniquely placed to understand the context in which they are working and identify their own training needs. Concept design, initial user research and subsequent ‘alpha’ and ‘private beta’ phase user research was conducted in a series of co-design iterations employing a mixed methodology integrating quantitative and qualitative data collection and analysis. Results User evaluation data demonstrated excellent feedback across the tested domains (content, navigation, likelihood of use and recommendation to colleagues). We identified several key themes from user testing that shaped the resource’s development. Conclusions The co-design approach to the development of this point-of-care genomics education resource for clinicians has allowed insight into the education needs, challenges and learning styles of end-users. The utility of this approach was supported by excellent user feedback across the tested domains, and we recommend it to others involved in developing healthcare resources in a fast-paced environment.

IntroductionA national genomics resource ‘GeNotes’ has been developed by NHS England Genomics Education Programme (GEP) to support routine implementation of genomic testing in clinical practice.1 GeNotes provides clinicians with information at the point of need, with opportunities for extended learning. The GeNotes resources consist of ‘In the Clinic’ scenarios (Tier 1), and a ‘Knowledge Hub’ (Tier 2) with resources including genetic conditions, genomic technologies and core concepts. Genomics resources have been launched across multiple specialties including cardiology, oncology and neurology, and now, also in Gastroenterology, and will assist our specialty in the provision of Genomic Service which is now in the ‘mainstreaming’ phase.MethodsIn June 2023 the Gastro-Hep working group (WG) was convened by co-chairs (KM and GPA), consisting of higher specialist resident doctors and specialist consultants with expertise (identified through the BSG and by the co-chairs) supported by a GeNotes Gastro-Hep Liaison (RS), and working with the GEP Education Development Lead (AF), with administrative support from the GEP. T1 and T2 resources were mapped to the NHS National Genomics Testing Directory. Additional resources were developed to support the application of genomics relevant to clinical practice, but which are outside existing testing directory indications, for example non-Mendelian risk for common diseases such as coeliac disease and IBD.ResultsTier 1 articles are centred around the point of patient care and feature a clinical scenario. Tier 2 acts as an encyclopaedia of resources that can be accessed either via links embedded in tier 1 or independently. The Gastro-Hep WG have produced 18 original Tier 1 ‘In the Clinic’ articles on topics including both gastroenterology (e.g. ‘A patient with polyposis’) and hepatology (e.g. ‘A patient with unexplained intrahepatic cholestasis’). We have also produced 7 original Tier 2 ‘Knowledge Hub’ resources, on topics ranging from serrated polyposis syndrome to polycystic liver disease.The WG has also co-produced a further 3 cross-speciality T1s and 10 T2s including oncology, paediatrics, pharmacogenomics and primary care. The Gastro-Hep GeNotes webpage official launch is late February 2025, however the WG will meet regularly to update the resources in future years. User feedback from website users will be collated and analysed to continue to improve user experience.ConclusionsPrevious evidence indicated a lack of confidence in delivery and interpretation of genomics by gastroenterologists.2 The first wave of Gastroenterology & Hepatology GeNotes resources is completed, providing specialty-specific guidance and resources to facilitate mainstreaming of genomic testing. Future iterations and amendments will be facilitated through the Gastroenterology WG.ReferencesGenotes – a ‘just-in-time’ genomics education resource co-designed with clinicians. Frost BMC Med Educ. 2024.Mainstreaming of genomic medicine in gastroenterology, present and future: a nationwide survey of UK gastroenterology trainees - PubMed. Al Bakir BMJ Open. 2019.

ObjectivesAs mainstreaming of genomic medicine is being implemented rapidly throughout paediatrics, it is critical that healthcare professionals are effectively upskilled in a timely fashion.1 Genomic Notes for Clinicians (GeNotes) is an NHS England National Genomics Education freely accessible online ‘just in time’ educational resource, designed to meet this need. It is aligned to the National Genomic Test Directory and supports clinicians, at the point of care, to identify when and how to request genomic tests and return results (‘In The Clinic’), and provides and extended learning opportunity (‘Knowledge Hub’). Paediatric content was launched on the public beta website in May 2023. We assessed usability, content and real-world use of the paediatric GeNotes resources.MethodsUsability testing took place in March 2022 and comprised user testing sessions in which participants completed a series of tasks using GeNotes by following a relevant clinical scenario. Data were collected via moderated user testing sessions, a feedback questionnaire and follow-up interviews. The sessions and interviews included a System Usability Scale (SUS) assessment.2 Live website analytics were undertaken to identify those pages most frequently accessed. Self-selection bias may affect the results as participants are likely to have a positive attitude towards genomics. We excluded IP addresses from National Genomics Education staff to avoid skewing the data on the pre-launch test site, however this was not possible for the live website.ResultsFive user testing sessions, 31 feedback surveys and 3 follow-up interviews were conducted. 61% of survey respondents were consultants and 39% were trainees working across quaternary, tertiary, secondary and community paediatrics across various UK regions. 91% said they would be likely or very likely to use GeNotes in the future. The mean SUS score was 86, indicating a high usability (the mean score for digital services is 68). Respondents reported that content is easy to navigate and appropriately detailed. Live website analytics identified that, between 14th June and 27th September 2023, there were 2,753 visits by 1,563 users to paediatric ‘In the Clinic’ pages, most frequently developmental delay/intellectual disability, macrocephaly, and suspected autism spectrum disorder.ConclusionUser testing suggests that GeNotes is a well-received, highly-usable educational resource appropriately pitched at paediatricians, which is being frequently accessed. Further work is required to expand the repository of resources in line with this rapidly evolving field, including resources to support Genomics England’s Generation Study, and to improve accessibility by exploring other routes of access, such as a mobile application.ReferencesAccelerating genomic medicine in the NHS, NHS England, 2022.Brooke J. SUS: A quick and dirty usability scale’ in Usability Evaluation in Industry, 1996.

Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders. Developmental disorders (DDs) are more prevalent in males, thought to be due to X-linked genetic variation. Here, the authors investigate the burden of X-linked coding variants in 11,044 DD patients, showing that this contributes to ~6% of both male and female cases and therefore does not solely explain male bias in DDs.

BackgroundClinical genetics is a small specialty with around 70 trainees nationally. New trainees traditionally have a period of observing clinics led by consultants and experienced genetic counsellors before leading their own clinic. This is an important time in which they learn practical and communication skills with respect to approaching a consultation, however, the experience can be variable dependent on the centre.In light of the coronavirus pandemic, knowing that many new trainees would not be able to access this vital induction period, we devised a virtual induction programme.MethodsA group of clinical geneticists from three UK centres, including GOSH, worked in collaboration with the GOSH Clinical Simulation Team to devise and deliver a programme that would be accessible to all new trainees. Important topics for discussion were agreed; example consultations were filmed, with the help of actors; and trainee simulations were planned.ResultsThe virtual induction runs live over two days, with homework, in the form of the filmed consultations that can be accessed at any time. The first day has been completed, delivering training to around 20 new trainees. The feedback we have received from both trainees and training programme directors has been overwhelmingly positive.DiscussionGiven the ongoing impact of the coronavirus pandemic, creative ways of delivering training are flourishing. We have created a bank of videos and presentations, as well as a template for future induction sessions, ensuring a basic level of equity between trainees at different genetics centres.ConclusionVirtual induction tools are a valuable and vital addition to new trainee induction to ensure equity of training, both during the current pandemic and beyond. This approach would work very well on a national level for other small specialties; or on a regional or local level for larger specialties.

Being able to separate ffDNA from maternal DNA will allow another new technique - array comparative genomic hybridisation - to look at foetal DNA in detail. This will mean earlier detection not only of gross genetic changes - such as the extra copy of chromosome 21 seen in Down's - but also of pathogenic microdeletions or microduplications.

Background Cornelia de Lange syndrome (CdLS) is a multisystem disorder with distinctive facial appearance, intellectual disability and growth failure as prominent features. Most individuals with typical CdLS have de novo heterozygous loss-of-function mutations in NIPBL with mosaic individuals representing a significant proportion. Mutations in other cohesin components, SMC1A, SMC3, HDAC8 and RAD21 cause less typical CdLS. Methods We screened 163 affected individuals for coding region mutations in the known genes, 90 for genomic rearrangements, 19 for deep intronic variants in NIPBL and 5 had whole-exome sequencing. Results Pathogenic mutations [including mosaic changes] were identified in: NIPBL 46 [3] (28.2%); SMC1A 5 [1] (3.1%); SMC3 5 [1] (3.1%); HDAC8 6 [0] (3.6%) and RAD21 1 [0] (0.6%). One individual had a de novo 1.3 Mb deletion of 1p36.3. Another had a 520 kb duplication of 12q13.13 encompassing ESPL1, encoding separase, an enzyme that cleaves the cohesin ring. Three de novo mutations were identified in ANKRD11 demonstrating a phenotypic overlap with KBG syndrome. To estimate the number of undetected mosaic cases we used recursive partitioning to identify discriminating features in the NIPBL-positive subgroup. Filtering of the mutation-negative group on these features classified at least 18% as ‘NIPBL-like’. A computer composition of the average face of this NIPBL-like subgroup was also more typical in appearance than that of all others in the mutation-negative group supporting the existence of undetected mosaic cases. Conclusions Future diagnostic testing in ‘mutation-negative’ CdLS thus merits deeper sequencing of multiple DNA samples derived from different tissues.