Evolution of genome diagnostics in epidermolysis bullosa: Unveiling the power of next‐generation sequencing

• DOI: 10.1111/jdv.19938
• Publication Date: 2024-03-11T09:20:01Z
• Authors: R. Baardman; H. H. Lemmink; V. K. Yenamandra; S. Z. Commandeur‐Jan; M. Viel; K. A. Kooi; G. F. H. Diercks; R. Meijer; M. van Geel; H. Scheffer; R. J. Sinke; B. Sikkema‐Raddatz; M. C. Bolling; P. C. van den Akker
• Keywords: Sanger sequencing; Molecular diagnostics; Gold standard (test)

Genome diagnostics is considered gold standard for epidermolysis bullosa (EB), a phenotypically and genetically heterogeneous group of rare disorders characterized by blistering wounding mucocutaneous tissues. EB caused pathogenic variants in genes encoding proteins the dermo-epidermal junction. Accurate genetic diagnosis crucial prognostication, counselling precision-medicine. started 1991 with introduction Sanger sequencing (SS), analysing one gene at time. In 2013, SS was superseded next-generation (NGS), that allow high-throughput multiple parallel. Several studies have shown beneficial role NGS diagnostics, but its true benefit has not been quantified. To determine systematically evaluating performance different genome used over time based on robust data from Dutch Registry. The diagnostic performances were evaluated retrospective observational study including all index cases clinical whom performed between 01 January 1994 2022 (n = 308), registered Expertise Centre. Over time, made 289/308 (94%) cases. yield increased 89% (SS) to 95% (NGS). Most importantly, significantly reduced turnaround (39 days vs. 211 days, p < 0.001). likelihood detecting uncertain significance additional findings 5% 1% 22% 13% (NGS) respectively. Our quantifies NGS-based methods demonstrate they had major impact through an dramatically decreased days). Although our high (95%), further improvement urgently needed provide patients.