Unknown

Dataset Information

0

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.

SUBMITTER: Krenn M 

PROVIDER: S-EPMC6916592 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

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

European journal of neurology 20190813 1


<h4>Background and purpose</h4>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.<h4>Methods</h4>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  ...[more]

Similar Datasets

| S-EPMC5798313 | biostudies-literature
| S-EPMC7216811 | biostudies-literature
| S-EPMC6084857 | biostudies-literature
| S-EPMC4669564 | biostudies-literature
| S-EPMC7182470 | biostudies-literature
| S-EPMC4286868 | biostudies-literature
| S-EPMC8528787 | biostudies-literature
| S-EPMC8595893 | biostudies-literature
| S-EPMC9034680 | biostudies-literature
| S-EPMC9876991 | biostudies-literature