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- Document type:
- Article
- Author(s):
- Krenn, M.; Tomschik, M.; Rath, J.; Cetin, H.; Grisold, A.; Zulehner, G.; Milenkovic, I.; Stogmann, E.; Zimprich, A.; Strom, T. M.; Meitinger, T.; Wagner, M.; Zimprich, F.
- Title:
- Genotype-guided diagnostic reassessment after exome sequencing in neuromuscular disorders: experiences with a two-step approach.
- 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.
- Journal title abbreviation:
- Eur J Neurol
- Year:
- 2020
- Journal volume:
- 27
- Journal issue:
- 1
- Pages contribution:
- 51-61
- Fulltext / DOI:
- doi:10.1111/ene.14033
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/31407473
- Print-ISSN:
- 1351-5101
- TUM Institution:
- Institut für Humangenetik
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