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Titel:

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

Dokumenttyp:
Article
Autor(en):
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.
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.
Zeitschriftentitel:
Eur J Neurol
Jahr:
2020
Band / Volume:
27
Heft / Issue:
1
Seitenangaben Beitrag:
51-61
Volltext / DOI:
doi:10.1111/ene.14033
PubMed:
http://view.ncbi.nlm.nih.gov/pubmed/31407473
Print-ISSN:
1351-5101
TUM Einrichtung:
Institut für Humangenetik
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