Biomedical subjects

Ann Nordgren

Publications and source records attributed to Ann Nordgren.

3 recordsLinked to original sources

PubMed2026

Phenotypic and transcriptomic characterization of biallelic RNU2-2 developmental and epileptic encephalopathy.

OBJECTIVE: A significant proportion of individuals with suspected genetic developmental and epileptic encephalopathies (DEEs) remain unsolved following whole genome sequencing (WGS). Here we describe biallelic RNU2-2 variants causing a recently reported, severe, recessive DEE. METHODS: We screened individuals who have received WGS analyses at the Genomic Medicine Centre Karolinska for Rare Diseases for biallelic RNU2-2 variants. Deep phenotyping was performed through reviewing entire medical histories and phenotypic traits were transcribed to their corresponding Human Phenotype Ontology (HPO) term. HPO terms were used to generate pairwise phenotypic similarity scores and assess for significantly shared phenotype enrichment in the RNU2-2 sub-cohort. RNA sequencing analyses were performed in fibroblast and blood tissues to compare splicing events between RNU2-2 individuals and two independent control groups. RESULTS: We identified 14 individuals from nine families with 12 ultra-rare biallelic RNU2-2 variants clustering in the conserved 5' domains. Genotype data from 13 of 14 individuals has been reported previously as part of a larger cohort. All individuals presented with a highly concordant, severe DEE, characterized by severe to profound intellectual disability, inability to walk or communicate, hyperkinesia, and refractory seizures. Infantile spasms and tonic seizures were the predominant seizure types and a Lennox-Gastaut syndrome-like phenotype was common. These individuals had a significantly similar phenotypic signature when compared with 703 individuals with complex pediatric epilepsies (two-sided Monte Carlo permutation test, p = .005). RNA sequencing analyses showed aberrant splicing, with the most pronounced effects in fibroblast tissues in mutually exclusive exon and alternate 3' splice-site events, which were not detectable in blood. SIGNIFICANCE: We present deep phenotyping data and transcriptomic analyses that provide support for rare, 5' clustering biallelic RNU2-2 variants causing this novel, severe DEE. We propose an RNA sequencing methodology on fibroblast tissue for future validation of RNU2-2 variants.

autosomal recessive disease↗

PubMed2026

Genomic Medicine Sweden: Advancing precision medicine at the national level.

High-throughput sequencing has transformed clinical diagnostics of rare diseases (RD), cancer and infectious diseases by enabling the identification of disease-causing genetic alterations and facilitating individualised treatment and care. In response to these advances, Genomic Medicine Sweden (GMS) was established in 2017 as a national collaborative effort to accelerate implementation of genomics-based precision medicine within Sweden's regionally organized, publicly funded healthcare system. GMS brings together the seven university healthcare regions and their associated medical faculties, in collaboration with healthcare regions across Sweden, Science for Life Laboratory, patient organizations, industry and governmental agencies. Activities are coordinated through national disease-specific expert groups, supported by cross-cutting functions in bioinformatics, health economics, ethics, education and patient engagement. At the operational level, seven Genomic Medicine Centres, embedded at university hospitals, develop and deliver harmonised genomic diagnostics nationwide. The National Genomics Platform provides secure infrastructure for large-scale data storage, analysis, and national and international data sharing. Following initial project-based funding, GMS now receives long-term governmental support. This review describes the national implementation of genomic-based precision diagnostics, discusses challenges and lessons learnt, and highlights key milestones across disease areas, including whole-genome sequencing in RD and paediatric cancer, comprehensive genomic profiling of haematological malignancies and solid tumours, pathogen genomics in microbiology, pharmacogenomic testing and emerging applications of polygenic risk scores in complex diseases. Collectively, these efforts have contributed to more than 500,000 genomic tests being performed within Swedish healthcare between 2017 and 2025. Finally, we outline future diagnostic needs and priority areas to ensure sustainable, scalable and equitable access to precision medicine.

Precision Medicine↗

PubMed2025

Mortality and Causes of Death in Boys and Men Born With Hypospadias: A Swedish Population-Based Cohort Study.

INTRODUCTION: Although hypospadias is not a life-threatening condition, studies have found perinatal factors and comorbidities which could increase mortality. We aimed to investigate mortality and causes of death in boys and men born with hypospadias. METHODS: We created a cohort of almost 3 million individuals including 16,890 with hypospadias using Swedish registers. We used Cox regression analysis to measure associations between hypospadias and all-cause mortality in different age groups (maximum age 65 years) as well as cause-specific mortality in adolescents and adults. RESULTS: We found associations between hypospadias and mortality in infancy (HR 2.07, 95% CI: 1.74-2.45), childhood (HR 1.77, CI: 1.34-2.33), and adolescence and adulthood (HR 1.31, CI: 1.11-1.56), with stronger associations for proximal hypospadias. Controlling for birth weight and congenital comorbidity significantly reduced the association in infancy. The association was lower in younger adults (HR 1.22, CI: 1.00-1.50) but increased again after age 35 years (HR 1.57, CI: 1.17-2.11). We found a significant association with death due to cardiovascular disease or diabetes (HR 3.20, CI: 1.93-5.32) and kidney or urological disease (HR 5.16, CI: 2.13-12.5), but not cancer overall, suicide, or accidents. CONCLUSIONS: While mortality overall was low, hypospadias is associated with relatively increased mortality from infancy to middle age. In early childhood, this is related to prenatal and perinatal factors. In adolescence and adulthood, the risk of death due to cardiovascular and urological disease was increased, providing further insight into long-term health in this patient group.

Humans↗