European Society Of Human Genetics Research Articles

Abstracts from the 56th European Society of Human Genetics (ESHG) Conference: Oral Presentations.

Abstracts from the 56th European Society of Human Genetics (ESHG) Conference: Oral Presentations.

Abstracts from the 56th European Society of Human Genetics (ESHG) Conference: e-Posters.

Abstracts from the 56th European Society of Human Genetics (ESHG) Conference: e-Posters.

Abstracts from the 56th European Society of Human Genetics (ESHG) Conference.

Abstracts from the 56th European Society of Human Genetics (ESHG) Conference.

Abstracts from the 56th European Society of Human Genetics (ESHG) Conference: Hybrid Posters.

Abstracts from the 56th European Society of Human Genetics (ESHG) Conference: Hybrid Posters.

Abstracts from the 55th European Society of Human Genetics (ESHG) Conference.

s from the 55th European Society of Human Genetics Conference: Oral PresentationsPlenary sessionsPL1 Opening PlenaryPL2 What’s New? Highlight SessionPL3 ELPAG Award LecturePL5 ESHG Award LectureConcurrent symposiaS01 Reproductive carrier screening in 2022S02 Methods for admixed populationsS03 Personalized care in breast cancer patientsS04 How do we deliver genomics education for all?S05 Chromothripsis and complex rearrangementsS06 Disorders of lysosomal biogenesis and autophagyS07 Cell lineages and organoidsS09 Mutation signaturesS10 Left/Right patterning/heterotaxyS11 Peopling the world: One archipelago at a timeS12 The genetics of omics and beyondS13 Unstable heritable genomic variations and cancer developmentS14 Predictive genetic counselling for neurodegenerative conditionsS15 Genetic architecture of the human faceS18 The importance of somatic variationS19 Polygenic scores: from methods to applicationsS20 Cross-cultural communication and counsellingS21 Translational genetics of boneS23 Non-coding RNAs in biology and diseaseS25 Multiomics for diagnosticsS26 Federation of genomic medicine databasesEducational sessionsE02 Genetics, 200 years after the births of Mendel and GaltonE04 ESHG-Y: Filling the gaps by publishing negative results in geneticsE05 MosaicismE06 Genetic discrimination: Surveying the ethico-legal landscapeE07 Progress of imputationE09 Pharmacogenomics for personalized drug treatmentE11 New treatments for congenital disordersE12 Inherited metabolic disorders with acute presentationsE14 Precision medicine in the digital health eraConcurrent sessionsC01 New genes in NDDsC02 Hereditary cancer syndromes and risk assessmentC03 Cellular differentiation and regulationC04 Unravelling causes and mechanisms of multiple congenital anomaliesC05 Population and Evolutionary GeneticsC06 Counselling, Education and Service DeliveryC07 Metabolic and mitochondrial diseasesC08 New findings for old NDD genesC09 Cardiac and neuromuscular geneticsC10 Internal organs and ImmunologyC11 New diagnostics and treatmentsC12 GWASC13 Patient Views on Clinical GeneticsC14 Late Breaking AbstractsC16 Prenatal GeneticsC17 Clinical impact of molecular tumor profilingC18 Machine learning, bioinformatics and biostatisticsC19 New gene defects and pathways in syndromic conditionsC20 Non-coding genome variation in Mendelian diseasesC21 Different strategies to unravel the genetic basis of NDDsC22 Innovation in genetic risk assessment and diagnosticsC24 Molecular mechanism in cancerC25 Reproductive GeneticsC26 New genes in multiple congenital anomaliesC27 New approaches and large datasets to unravel human traitsC28 Novel neurogenetic disordersC29 Eye Genetics

Abstracts from the 55th European Society of Human Genetics (ESHG) Conference: Hybrid Posters

Abstracts from the 55th European Society of Human Genetics (ESHG) Conference: Hybrid Posters

Abstracts from the 55th European Society of Human Genetics (ESHG) Conference: Oral Presentations.

C14 Late Breaking AbstractsC14.1 Progressive liver, kidney and heart degeneration in adults affected by TULP3 mutationsElisabeth Ott1, John Devane1, Eric G. Olinger2, Daniel Epting1, Eva Decker3, Anja Friedrich3, Nadine Bachmann3, Gina Renschler3, Tobias Eisenberger3, Genomics England Research Consortium4, Inga Gruenewald5, Martin Konrad6, Jens König6, Bernhard Schlevogt7, John Sayer8, Carsten Bergmann 1;3 1Department of Medicine IV, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany; 2Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, United Kingdom; 3Medizinische Genetik Mainz, Mainz, Germany; 4Genomics England Research Consortium, London, Germany; 5Institute for Pathology, University Hospital Münster, Münster, Germany; 6Department of General Pediatrics, University Hospital Münster, Münster, Germany; 7Department of Internal Medicine B, Gastroenterology, University Hospital Münster, Münster, Germany; 8Renal Services, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom Background/Objectives: Organ fibrosis is an endpoint of many diseases. Ciliopathies usually start early in life and represent a considerable disease burden in paediatric patients. Methods: We performed NGS, clinical, imaging and histopathological analysis involving eight unrelated families. Mechanistic studies were conducted using patient liver, heart and kidney biopsies, a vertebrate model and patient cells. Results: We detected biallelic deleterious variants in TULP3, a critical adapter protein for ciliary trafficking, in 15 patients who presented with progressive degenerative disease in different organs including fibrocystic kidney disease, liver fibrosis and hypertrophic cardiomyopathy. Liver biopsies revealed a distinct fibrotic pattern not in line with ductal plate malformation usually seen in paediatric ciliopathies and myocardial fibrosis followed an atypical pattern reminiscent of systemic disease with cardiac involvement. We recapitulated the human phenotype in zebrafish as a vertebrate model and confirmed disruption of ciliary cargo composition in patient-derived primary cells. Additionally, we validated a novel interaction between TULP3 and the nuclear deacetylase SIRT1, with roles in DNA damage repair and fibrosis. Increased levels of DNA damage were also seen in patient cells. Patient-cell based transcriptomic studies highlighted the upregulation of profibrotic pathways with gene clusters for hypertrophic cardiomyopathy, WNT and TGFß signalling. Conclusion: These findings identify a novel monogenic cause for progressive degenerative disease of major organs in which patients benefit from early detection and improved clinical management. Elucidation of mechanisms crucial for well-balancing DNA-damage repair and tissue maintenance will help guiding novel therapeutic avenues for this and similar genetic and non-genomic diseases.

Abstracts from the 55th European Society of Human Genetics (ESHG) Conference: e-Posters

Abstracts from the 55th European Society of Human Genetics (ESHG) Conference: e-Posters

Abstracts from the 54th European Society of Human Genetics (ESHG) Conference.

s from the 54th European Society of Human Genetics Conference: oral presentationsPlenary sessionsPL1 Opening PlenaryPL2 What’s New? Highlight SessionPL4 Mendel Award LectureConcurrent symposiaS01 Machine learning methods for prioritising genetic variantsS02 Spatial omicsS03 TransposonsS04 Impact of GDPR on genomic data sharingS05 Endogenous and exogenous mutagenesis in cancerS06 Comparative genomics across species and populationsS07 Mind the gap: Translating genomic advances into clinical careS08 Single cell genomics in cancerS09 Biobanks in under-represented populationsS10 Gene-based therapy for inherited liver diseasesS11 Prevention, detection, and therapy in cancerS12 Functional annotation of genomic variationS13 Beauty of gametogenesisS14 Genome architectureS15 Cells competing cells - mosaicism and cancerS16 ESHG-ASHG Building Bridges: Global genetics towards a socially just practiceS17 Biases in genetic studies: Estimation and impactS18 Overgrowth syndromes, from discovery to therapyS20 Counselling Over Various Informatic Devices: Lessons from Covid-19S21 Delivering the promise of RNA therapeuticsS22 Integrated approaches for ciliopathiesEducational sessionsE01 New technologiesE02 ESHG-Y: Human organoids as genetic disease modelsE03 Translational collaborations in hereditary cancerE04 Dealing with uncertainty in genomic medicineE05 Update on imprinting disordersE06 Pharmacogenomics in the clinicE08 Variant interpretation in the clinicE09 What’s new in preimplantation genetic testing?E11 Polygenic risks and meE12 Bayesian methods applied in clinical settingsE13 Mapping the human body at the cellular levelE14 DNA methylation in Mendelian diseasesE15 Selection and population structure in biobank scale dataE16 Advances in Mendelian randomisationE17 Chromosomal instability across lifetimeE18 Introduction to statistical analysis of genome-wide association studies (GWAS)E19 Precision medicine in underserved populationsConcurrent sessionsC01 Developmental disorders & syndromes IC02 Cardiovascular disordersC03 Bioinformatics, machine learning and statistical methodsC04 Unraveling the complexity of neuropsychiatric geneticsC05 Reproduction is hot!C06 COVID-19 GenomicsC07 Novel insights in inherited metabolic diseasesC08 Skeletal and connective tissue disordersC09 Sensory disorders: multi-omics and long-read sequencingC10 Genome-wide Association StudiesC11 New technologies and better diagnosticsC12 Counselling, communication and service deliveryC13 Cancer susceptibility: From mechanisms to clinicC14 Advances in neurogenetics: From diagnosis to treatmentC15 Pleiotropic diseases: diagnosis and mechanismsC16 Monogenic neurodevelopmental disordersC17 Population genetics and genetic epidemiologyC18 Functional genomics and transcriptomicsC19 ELSI in genomicsC20 From mechanisms to therapeutic insights in cancerC21 Clinical immunology and novel therapies of genetic diseasesC22 Developmental disorders & syndromes IIC23 Internal organs - Kidney, bowel, fatC24 Genome variation and architectureC25 Using genomics to personalise medicineC26 Late Breaking

Recommendations for reporting results of diagnostic genomic testing

Results of clinical genomic testing must be reported in a clear, concise format to ensure they are understandable and interpretable. It is important laboratories are aware of the information which is essential to make sure the results are not open to misinterpretation. As genomic testing has continued to evolve over the past decade, the European Society of Human Genetics (ESHG) recommendations for reporting results of diagnostic genetic testing (biochemical, cytogenetic and molecular genetic) published in 2014 have been reviewed and updated to provide the genomic community with guidance on reporting unambiguous results.

Abstracts from the 54th European Society of Human Genetics (ESHG) Conference: e-Posters.

Abstracts from the 54th European Society of Human Genetics (ESHG) Conference: e-Posters.

Abstracts from the 54th European Society of Human Genetics (ESHG) Conference: Oral Presentations.

Abstracts from the 54th European Society of Human Genetics (ESHG) Conference: Oral Presentations.

The Role of the European Society of Human Genetics in Delivering Genomic Education.

The European Society of Human Genetics (ESHG) was founded in 1967 as a professional organisation for members working in genetics in clinical practice, research and education. The Society seeks the integration of scientific research and its implementation into clinical practice and the education of specialists and the public in all areas of medical and human genetics. The Society works to do this through many approaches, including educational sessions at the annual conference; training courses in general and specialist areas of genetics; an online resource of educational materials (EuroGEMS); and a mentorship scheme. The ESHG Education Committee is implementing new approaches to expand the reach of its educational activities and portfolio. With changes in technology, appreciation of the utility of genomics in healthcare and the public’s and patients’ increased awareness of the role of genomics, this review will summarise how the ESHG is adapting to deliver innovative educational activity.

Creation and Worldwide Utilisation of New COVID-19 Online Information Hub for Genetics Health Professionals, Patients and Families.

The current COVID-19 pandemic has unfortunately resulted in many significant concerns for individuals with genetic disorders and their relatives, regarding the viral infection and, particularly, its specific implications and additional advisable precautions for individuals affected by genetic disorders. To address this, the resulting requirement for guidance and information for the public and for genetics professionals was discussed among colleagues nationally, on the ScotGEN Steering Committee, and internationally on the Education Committee of the European Society of Human Genetics (ESHG). It was agreed that the creation of an online hub of genetics-related COVID-19 information resources would be particularly helpful. The proposed content, divided into a web page for professionals and a page for patients, was discussed with, and approved by, genetics professionals. The hub was created and provided online at www.scotgen.org.uk and linked from the ESHG’s educational website for genetics and genomics, at www.eurogems.org. The new hub provides links, summary information and representative illustrations for a wide range of selected international resources. The resources for professionals include: COVID-19 research related hubs provided by Nature, Science, Frontiers, and PubMed; clinical guidelines; the European Centre for Disease Prevention and Control; the World Health Organisation; and molecular data sources including coronavirus 3D protein structures. The resources for patients and families include links to many accessible sources of support and relevant information. Since the launch of the pages, the website has received visits from over 50 countries worldwide. Several genetics consultants have commented on usefulness, clarity, readability, and ease of navigation. Visits have originated most frequently in the United Kingdom, Kuwait, Hong Kong, Moldova, United States, Philippines, France, and Qatar. More links have been added since the launch of the hub to include additional international public health and academic resources. In conclusion, an up-to-date online hub has been created and made freely available for healthcare professionals, patients, relatives and the public, providing categorised easily navigated links to a range of worldwide resources related to COVID-19. These pages are receiving a rapidly growing number of return visits and the authors continue to maintain and update the pages’ content, incorporating new developments in this field of enormous worldwide importance.

Does the law require reinterpretation and return of revised genomic results?

Does the law require reinterpretation and return of revised genomic results?

The impact of needs-based education on the change of knowledge and attitudes towards medical genetics in medical students.

In this research we aimed to (1) develop and validate a new questionnaire examining attitudes and knowledge towards medical genetics, (2) examine the knowledge and attitudes towards medical genetics in students of the Medical Faculty in Rijeka, Croatia and (3) evaluate the impact of education from the mandatory course Medical Genetics on the change of knowledge and attitudes. The study was conducted on 191 fifth- and sixth-year students of the Integrated Undergraduate and Graduate University Study of Medicine in the academic year 2019/2020. Students completed the validated online questionnaire anonymously and voluntarily. Fifth-year students completed the questionnaire twice (beginning/end of the course), while sixth-year students completed the questionnaire once, 3 months after completing the course. The education was carefully designed for medical students according to the CoreCompetences in Genetics for Health Professionals in Europe issued by the European Society of Human Genetics. Using the Kruskal-Wallis test, a statistically significant difference was found between fifth year before and after education and between the fifth year before education and sixth year for (a) total knowledge (P < 0.001), (b) total attitudes (P < 0.001) and (c) personal assessment of knowledge in medical genetics (P < 0.001). Moreover, positive attitudes were associated with higher levels of knowledge. In conclusion, our results emphasise the importance of needs-based education in medical genetics for medical students, which is indispensable for the increase in the level of knowledge and development of positive attitudes in order to provide better health care for patients with genetic disorders.

European Society of Human Genetics (ESHG) Conference. Virtual - August 28-31, 2021

European Society of Human Genetics (ESHG) Conference. Virtual - August 28-31, 2021

Sanger Validation of High-Throughput Sequencing in Genetic Diagnosis: Still the Best Practice?

Next-generation sequencing (NGS)’s crucial role in supporting genetic diagnosis and personalized medicine leads to the definition of Guidelines for Diagnostic NGS by the European Society of Human Genetics. Factors of different nature producing false-positive/negative NGS data together with the paucity of internationally accepted guidelines providing specified NGS quality metrics to be followed for diagnostics purpose made the Sanger validation of NGS variants still mandatory. We reported the analysis of three cases of discrepancy between NGS and Sanger sequencing in a cohort of 218 patients. NGS was performed by Illumina MiSeq® and Haloplex/SureSelect protocols targeting 97 or 57 or 10 gene panels usually applied for diagnostics. Variants called following guidelines suggested by the Broad Institute and identified according to MAF <0.01 and allele balance >0.2 were Sanger validated. Three out of 945 validated variants showed a discrepancy between NGS and Sanger. In all three cases, a deep evaluation of the discrepant gene variant results and methodological approach allowed to confirm the NGS datum. Allelic dropout (ADO) occurrence during polymerase chain or sequencing reaction was observed, mainly related to incorrect variant zygosity. Our study extends literature data in which almost 100% “high quality” NGS variants are confirmed by Sanger; moreover, it demonstrates that in case of discrepancy between a high-quality NGS variant and Sanger validation, NGS call should not be a priori assumed to represent the source of the error. Actually, difficulties (i.e., ADO, unpredictable presence of private variants on primer-binding regions) of the so-called gold standard direct sequencing should be considered especially in light of the constantly implemented and accurate high-throughput technologies. Our data along with literature raise a discussion on the opportunity to establish a standardized quality threshold by International Guidelines for clinical NGS in order to limit Sanger confirmation to borderline conditions of variant quality parameters and verification of correct gene variant call/patient coupling on a different blood sample aliquot.

Abstracts from the 53rd European Society of Human Genetics (ESHG) Conference: Interactive e-Posters.

Abstracts from the 53rd European Society of Human Genetics (ESHG) Conference: Interactive e-Posters.

Abstracts from the 53rd European Society of Human Genetics (ESHG) Conference: Oral Presentations.

Abstracts from the 53rd European Society of Human Genetics (ESHG) Conference: Oral Presentations.