ArticleGenome medicine2021
Integration of whole genome sequencing into a healthcare setting: high diagnostic rates across multiple clinical entities in 3219 rare disease patients.
Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers, 2 of them syntheses that pooled it.
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Who cites it
166 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Measuring the health benefits of genome and exome sequencing: a systematic review of economic evaluations.Frontiers in public health · 2025Pooled it
- Prenatal Genome-Wide Sequencing analysis (Exome or Genome) in detecting pathogenic Single Nucleotide Variants in fetal Central Nervous System Anomalies: systematic review and meta-analysis.European journal of human genetics : EJHG · 2024Pooled it
- Genome sequencing for the diagnosis of intellectual disability as a paradigm for rare diseases in the French healthcare setting: the prospective DEFIDIAG study.Genome medicine · 2025Trial
- Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study.BMJ (Clinical research ed.) · 2021Trial
- Genomic Medicine Sweden: Advancing precision medicine at the national level.Journal of internal medicine · 2026Review
- Diagnostic yield of cancer predisposition in a nationwide prospective childhood acute leukemia cohort.Nature communications · 2026Article
- Article
- Advances in diagnosis of mitochondrial dysfunction and primary mitochondrial disease.Disease models & mechanisms · 2026Review
- Clinical genome sequencing in neurodegenerative diseases-outcome in the first 500 patients.Human molecular genetics · 2026Article
- Systematic reanalysis of next-generation sequencing data in 101 neuromuscular disorder families enhances diagnostic yield, reveals intronic variants, and identifies a novel disease gene.Journal of neurology · 2026Article
- RankVar: machine learning-based variant ranking and reinterpretation for rare genetic diseases.Genome medicine · 2026Article
- MRPS22 variants alter mitochondrial ribosome assembly in patients with leukodystrophy, movement disorder and intellectual impairment.Human molecular genetics · 2026Article
- Fatal European subtype tick-borne encephalitis in a fully vaccinated immunocompetent child: a case report with viral sequencing.BMC infectious diseases · 2026Article
- Rare variants in TTC7A, ROCK2 and LIMK2 suggest a role for the ROCK-signaling pathway in isolated intestinal malrotation.Pediatric surgery international · 2026Article
- Determinants of DNA-sequence-based Diagnostic Yield in the CSER Consortium.medRxiv : the preprint server for health sciences · 2026Article
- Diagnostic yield and genetic landscape of rare pediatric diseases in Vietnam identified by exome sequencing.Scientific reports · 2026Article
- The genomic medicine center Karolinska 10-year report on genome sequencing for rare diseases and a strategy for stepwise clinical implementation.Genome medicine · 2026Article
- A novel phenotype-guided genome analysis pipeline for variant discovery.NPJ genomic medicine · 2026Article
- Implementing Genomic Medicine in Primary Care: A Convergent Mixed Method Case Study.Journal of evaluation in clinical practice · 2026Article
- Nallo: a Nextflow pipeline for comprehensive human long-read genome analysis.Bioinformatics (Oxford, England) · 2026Article
106 more citing papers are in PubMed but not listed here.
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52 authors.
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Abstract
backgroundWe report the findings from 4437 individuals (3219 patients and 1218 relatives) who have been analyzed by whole genome sequencing (WGS) at the Genomic Medicine Center Karolinska-Rare Diseases (GMCK-RD) since mid-2015. GMCK-RD represents a long-term collaborative initiative between Karolinska University Hospital and Science for Life Laboratory to establish advanced, genomics-based diagnostics in the Stockholm healthcare setting.
methodsOur analysis covers detection and interpretation of SNVs, INDELs, uniparental disomy, CNVs, balanced structural variants, and short tandem repeat expansions. Visualization of results for clinical interpretation is carried out in Scout-a custom-developed decision support system. Results from both singleton (84%) and trio/family (16%) analyses are reported. Variant interpretation is done by 15 expert teams at the hospital involving staff from three clinics. For patients with complex phenotypes, data is shared between the teams.
resultsOverall, 40% of the patients received a molecular diagnosis ranging from 19 to 54% for specific disease groups. There was heterogeneity regarding causative genes (n = 754) with some of the most common ones being COL2A1 (n = 12; skeletal dysplasia), SCN1A (n = 8; epilepsy), and TNFRSF13B (n = 4; inborn errors of immunity). Some causative variants were recurrent, including previously known founder mutations, some novel mutations, and recurrent de novo mutations. Overall, GMCK-RD has resulted in a large number of patients receiving specific molecular diagnoses. Furthermore, negative cases have been included in research studies that have resulted in the discovery of 17 published, novel disease-causing genes. To facilitate the discovery of new disease genes, GMCK-RD has joined international data sharing initiatives, including ClinVar, UDNI, Beacon, and MatchMaker Exchange.
conclusionsClinical WGS at GMCK-RD has provided molecular diagnoses to over 1200 individuals with a broad range of rare diseases. Consolidation and spread of this clinical-academic partnership will enable large-scale national collaboration.
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