Genotype-guided diagnostic reassessment after exome sequencing in neuromuscular disorders: experiences with a two-step approach

M. Krenn, M. Tomschik, J. Rath, H. Cetin, A. Grisold, G. Zulehner, I. Milenkovic, E. Stogmann, A. Zimprich, T. M. Strom, T. Meitinger, M. Wagner, F. Zimprich

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

23 Zitate (Scopus)

Abstract

Background and purpose: Next-generation sequencing has greatly improved the diagnostic success rates for genetic neuromuscular disorders (NMDs). Nevertheless, most patients still remain undiagnosed, and there is a need to maximize the diagnostic yield. Methods: A retrospective study was conducted on 72 patients with NMDs who underwent exome sequencing (ES), partly followed by genotype-guided diagnostic reassessment and secondary investigations. The diagnostic yields that would have been achieved by appropriately chosen narrow and comprehensive gene panels were also analysed. Results: The initial diagnostic yield of ES was 30.6% (n = 22/72 patients). In an additional 15.3% of patients (n = 11/72) ES results were of unknown clinical significance. After genotype-guided diagnostic reassessment and complementary investigations, the yield was increased to 37.5% (n = 27/72). Compared to ES, targeted gene panels (<25 kilobases) reached a diagnostic yield of 22.2% (n = 16/72), whereas comprehensive gene panels achieved 34.7% (n = 25/72). Conclusion: Exome sequencing allows the detection of pathogenic variants missed by (narrowly) targeted gene panel approaches. Diagnostic reassessment after genetic testing further enhances the diagnostic outcomes for NMDs.

OriginalspracheEnglisch
Seiten (von - bis)51-61
Seitenumfang11
FachzeitschriftEuropean Journal of Neurology
Jahrgang27
Ausgabenummer1
DOIs
PublikationsstatusVeröffentlicht - 1 Jan. 2020

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