Karolinska 10-Year Rare Disease Sequencing Study Published as WES Meta-Analysis Shows 37% Diagnostic Yield

Karolinska Institute published a 10-year implementation study of clinical genome sequencing for rare diseases, GenomeWeb and 360Dx reported. The study arrives alongside multiple datasets that quantify diagnostic yields and platform limitations for genomic testing in clinical practice.

A meta-analysis of 102 studies covering 55,752 children with global developmental delay or intellectual disability found whole exome sequencing delivered a pooled diagnostic yield of 37% (95% CI: 33–41%), with superior diagnostic and clinical utility compared to chromosomal microarray, according to the study. The figure gives payers a benchmark for first-tier testing decisions in pediatric rare disease workups.

Foundation Medicine's FoundationOne Liquid CDx detected H3K27M mutations in diffuse midline glioma at 2.8% versus 92.2% for the tissue-based F1 CDx assay (p<0.01) across 114 patients, per the study. The gap reflects the blood-brain barrier's effect on circulating tumor DNA shedding and indicates liquid biopsy sensitivity limitations in central nervous system malignancies.

Oxford Nanopore Technologies received regulatory approval for its first diagnostic device in the UK and Europe. A study of nanopore sequencing for nontuberculous mycobacterial pulmonary disease diagnosis across 871 patients reported 93.3% sensitivity and 97.2% specificity with an AUC of 0.95, per the published data.

A meta-analysis of 13 multi-cancer early detection studies covering 14,892 participants found machine learning models achieved pooled sensitivity of 78% (95% CI: 66–87%) and specificity of 96% (95% CI: 90–98%), with summary AUC of 0.94 and diagnostic odds ratio of 76.6 in independent validation datasets, according to the analysis. The wide sensitivity confidence interval indicates heterogeneity across cancer types.

Additional studies reported a DNA methylation test (WID-qEC) detected recurrent endometrial cancer in 62.5% of cervico-vaginal samples and 58.8% of urine samples, per the research. The CHARM2 randomized controlled trial is enrolling 1,000 participants with hereditary cancer syndromes to compare cell-free DNA screening against conventional surveillance, per the trial record.