Detection of clinically relevant variants in the gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL.

In chronic lymphocytic leukemia, the reliability of next-generation sequencing (NGS) to detect variants ≤10% allelic frequency (low-VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.

Impact of TCF7L2 rs7903146 on clinical presentation and risk of complications in patients with type 2 diabetes.

Aims: TCF7L2 rs7903146 is the most impactful single genetic risk variant for type 2 diabetes. However, its role on disease progression, complications and mortality among people with type 2 diabetes at diagnosis remains unclear.

Materials And Methods: We assessed the per allele impact of the rs7903146 T-allele on clinical characteristics and complication risk in 9231 individuals with type 2 diabetes at diagnosis and over a 10-year follow-up period.

The Danish Centre for Strategic Research in Type 2 Diabetes (DD2) Project Cohort and Biobank from 2010 Through 2023-A Cohort Profile Update.

Purpose: This paper provides an overview of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort and biobank, including baseline characteristics of participants enrolled up to 2023, and post-enrollment rates of cardiovascular disease outcomes and mortality.

Methods: Since 2010, the DD2 project has enrolled individuals with type 2 diabetes mellitus (T2DM) recently diagnosed by general practitioners and by hospital-based clinicians across Denmark. Data from questionnaires, clinical examinations, and biological samples are collected at enrollment.

How to manage patients with germline variants: Recommendations from the Nordic working group on germline predisposition for myeloid neoplasms.

Increasing recognition of germline variants in patients with hematological malignancies prompted us to provide -specific recommendations for diagnosis, surveillance, and treatment. Causative germline variants in the predispose to the development of myeloid neoplasms (MNs), especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Almost 3%-5% of all patients with MDS or AML carry a pathogenic or likely pathogenic germline variant, while half of them acquire a somatic second hit in the other allele.

Vision-related quality of life, photoaversion, and optical rehabilitation in achromatopsia.

Significance: We report on photoaversion and patient-reported quality of life in Danish patients with achromatopsia and evaluate the best optical rehabilitation. Our results contribute to the evaluation of outcome measures in therapy trials and aid in providing the best optical rehabilitation for patients with this and clinically similar conditions.

Purpose: This study aimed to investigate the vision-related quality of life, the impact of photoaversion on daily living, and the best optical rehabilitation in a cohort of achromatopsia patients, including testing the hypothesis that red light-attenuating filters are generally preferred.

Analysis of admixed Greenlandic siblings shows that the mean genotypic values for metabolic phenotypes differ between Inuit and Europeans.

Background: Disease prevalence and mean phenotype values differ between many populations, including Inuit and Europeans. Whether these differences are partly explained by genetic differences or solely due to differences in environmental exposures is still unknown, because estimates of the genetic contribution to these means, which we will here refer to as mean genotypic values, are easily confounded, and because studies across genetically diverse populations are lacking.

Methods: Leveraging the unique genetic properties of the small, admixed and historically isolated Greenlandic population, we estimated the differences in mean genotypic value between Inuit and European genetic ancestry using an admixed sibling design.

Low birthweight in patients with type 2 diabetes is associated with elevated risk of cardiovascular events and mortality.

Aims/hypothesis: Low birthweight is a risk factor for type 2 diabetes and CVD. This prospective cohort study investigated whether lower birthweight increases CVD risk after diagnosis of type 2 diabetes.

Methods: Original midwife records were evaluated for 8417 participants recently diagnosed with type 2 diabetes in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort.

Children born preterm or small for gestational age to mothers with multiple sclerosis: Do these children have an increased risk of infections in early life?

Background: Mothers with multiple sclerosis are at increased risk of preterm birth and small for gestational age infants. Both conditions pose a risk of morbidity, including early-life infections.

Objective: This study aimed to assess the risk of infections in the first 3 years of life among children born preterm or small for gestational age to mothers with multiple sclerosis.

Expanding the understanding of telomere biology disorder with reports from two families harboring variants in ZCCHC8 and TERC.

Telomere biology disorder (TBD) can present within a wide spectrum of symptoms ranging from severe congenital malformations to isolated organ dysfunction in adulthood. Diagnosing TBD can be challenging given the substantial variation in symptoms and age of onset across generations. In this report, we present two families, one with a pathogenic variant in ZCCHC8 and another with a novel variant in TERC.

Characterization of the gut bacterial and viral microbiota in latent autoimmune diabetes in adults.

Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease characterized by autoantibodies against insulin producing pancreatic beta cells and initial lack of need for insulin treatment. The aim of the present study was to investigate if individuals with LADA have an altered gut microbiota relative to non-diabetic control subjects, individuals with type 1 diabetes (T1D), and individuals with type 2 diabetes (T2D). Bacterial community profiling was performed with primers targeting the variable region 4 of the 16S rRNA gene and sequenced.

Neonatal outcomes in women with Multiple Sclerosis - Influence of disease activity: A Danish nationwide cohort study.

Background: Maternal Multiple Sclerosis (MS) has been associated with an increased risk of adverse birth outcomes. We hypothesized that active disease during conception and pregnancy plays an important role in this context, which this study aims to address.

Methods: We used the Danish registers to conduct a nationwide cohort study.

Low-grade inflammation in persons with recently diagnosed type 2 diabetes: The role of abdominal adiposity and putative mediators.

Aims: To determine the magnitude of the association between abdominal adiposity and low-grade inflammation in persons with recently diagnosed type 2 diabetes (T2D) and to determine to what extent this association is mediated by low physical activity level, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, hypertension, and comorbidities.

Materials And Methods: We measured waist circumference, clinical characteristics, and inflammatory markers i.e.

Phenotypic characteristics of Danish patients with achromatopsia.

Purpose: To describe the phenotype of Danish patients with genetically verified achromatopsia (ACHM) with special focus on signs of progression on structural or functional parameters, and possible genotype-phenotype correlations.

Methods: Forty-eight patients were identified, with disease-causing variants in five different genes: CNGA3, CNGB3, GNAT2, PDE6C and PDE6H. Longitudinal evaluation was possible for 11 patients and 27 patients participated in a renewed in-depth phenotyping consisting of visual acuity assessment, optical coherence tomography (OCT), fundus autofluorescence, colour vision evaluation, contrast sensitivity, mesopic microperimetry and full-field electroretinography.

Risk of cancer in relatives of patients with myelodysplastic neoplasia and acute leukemias.

Background: The risk of cancer among relatives of patients with either myelodysplastic neoplasia (MDS), acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) has not been thoroughly examined.

Methods: We linked the Danish Civil Registration System with the Danish Cancer Registry, the Danish National Acute Leukemia Registry, and the Danish Myelodysplastic Syndrome Database to estimate the relative risk of cancer among relatives of patients with MDS/AML/ALL. We used standardized incidence ratios (SIRs), i.

Atorvastatin for patients with cirrhosis. A randomized, placebo-controlled trial.

Background: Patients with cirrhosis and portal hypertension face a high risk of complications. Besides their anti-inflammatory and antifibrotic effects, statins may reduce portal pressure and thus the risk of complications and mortality. We aimed to investigate the effects of atorvastatin on hospital admissions, mortality, inflammation, and lipidomics in cirrhosis with portal hypertension.

Genetics of metabolic traits in Greenlanders.

The history of the Greenlandic population has contributed to a unique genetic composition in which high-impact and often novel genetic variants segregate at a high frequency. As a result, research in smaller populations like the Greenlandic has the potential to reveal genetic variation and associations that are not present or discoverable in other populations. In this review, we provide a summary of our research in Greenlanders and our findings of genetic variants with high impact on metabolic health, and outline the implications that this research has for the equitable distribution of genomic precision medicine.

National clinical Genetic Networks - GENets - Establishment of expert collaborations in Denmark.

Genetic conditions are often familial, but not all relatives receive counseling from the same institution. It is therefore necessary to ensure consistency in variant interpretation, counseling practices, and clinical follow up across health care providers. Furthermore, as new possibilities for gene-specific treatments emerge and whole genome sequencing becomes more widely available, efficient data handling and knowledge sharing between clinical laboratory geneticists and medical specialists in clinical genetics are increasingly important.

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The Danish Health Authority recommends that all patients with life threatening disease, regardless of the diagnosis, are offered palliative care with respect for individual goals of care. Only few studies have investigated the evidence of ACP in patients with decompensated liver cirrhosis. This review defines ways to identify patients with decompensated liver cirrhosis in need of palliative care and how to analyse the goals of care.

Precision subclassification of type 2 diabetes: a systematic review.

Background: Heterogeneity in type 2 diabetes presentation and progression suggests that precision medicine interventions could improve clinical outcomes. We undertook a systematic review to determine whether strategies to subclassify type 2 diabetes were associated with high quality evidence, reproducible results and improved outcomes for patients.

Methods: We searched PubMed and Embase for publications that used 'simple subclassification' approaches using simple categorisation of clinical characteristics, or 'complex subclassification' approaches which used machine learning or 'omics approaches in people with established type 2 diabetes.