Dataset Information

Usefulness of comprehensive targeted multigene panel sequencing for neuromuscular disorders in Korean patients.

ABSTRACT:

Background

Multigene panel sequencing (MGPS) is the first-line option in diagnostic testing for genetically heterogeneous but clinically similar conditions, such as neuromuscular disorders (NMDs). In this study, we aimed to assess the utility of comprehensive NMD MGPS and the need for updated panels.

Methods

All patients were analyzed by either of two versions of the NMD MGPS and by chromosomal microarray and karyotype testing. Four patients with negative NMD MGPS results underwent whole exome sequencing.

Results

In total, 91 patients were enrolled, and a genetic diagnosis was made in 36 (39.6%); of these, 33 were diagnosed by the comprehensive NMD MGPS, two were confirmed by chromosomal microarray, and one was diagnosed by whole exome sequencing. For MGPS, the diagnostic yield of Version 2 (19/52; 36.5%) was a little higher than that of Version 1 (14/39; 35.9%), and one gene identified in Version 2 was not included in Version 1. A total of 36 definitive and nine possible causative variants were identified, of which 17 were novel.

Conclusion

A more comprehensive panel for NMD MGPS can improve the diagnostic efficiency in genetic testing. The rapid discovery of new disease-causing genes over recent years necessitates updates to existing gene panels.

SUBMITTER: Park J

PROVIDER: S-EPMC6785438 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Publications

Usefulness of comprehensive targeted multigene panel sequencing for neuromuscular disorders in Korean patients.

Park Jihye J Oh Hyun Mi HM Park Hye Jung HJ Cho Ah-Ra AR Lee Dong-Woo DW Jang Ja-Hyun JH Jang Dae-Hyun DH

Molecular genetics & genomic medicine 20190901 10

<h4>Background</h4>Multigene panel sequencing (MGPS) is the first-line option in diagnostic testing for genetically heterogeneous but clinically similar conditions, such as neuromuscular disorders (NMDs). In this study, we aimed to assess the utility of comprehensive NMD MGPS and the need for updated panels.<h4>Methods</h4>All patients were analyzed by either of two versions of the NMD MGPS and by chromosomal microarray and karyotype testing. Four patients with negative NMD MGPS results underwen ...[more]

PMID: 31475473

Similar Datasets

Project description:BACKGROUND:As DNA sequencing costs decline, genetic testing options have expanded. Whole exome sequencing and whole genome sequencing (WGS) are entering clinical use, posing questions about their incremental value compared with disease-specific multigene panels that have been the cornerstone of genetic testing. METHODS AND RESULTS:Forty-one patients with hypertrophic cardiomyopathy who had undergone targeted hypertrophic cardiomyopathy genetic testing (either multigene panel or familial variant test) were recruited into the MedSeq Project, a clinical trial of WGS. Results from panel genetic testing and WGS were compared. In 20 of 41 participants, panel genetic testing identified variants classified as pathogenic, likely pathogenic, or uncertain significance. WGS identified 19 of these 20 variants, but the variant detection algorithm missed a pathogenic 18 bp duplication in myosin binding protein C (MYBPC3) because of low coverage. In 3 individuals, WGS identified variants in genes implicated in cardiomyopathy but not included in prior panel testing: a pathogenic protein tyrosine phosphatase, non-receptor type 11 (PTPN11) variant and variants of uncertain significance in integrin-linked kinase (ILK) and filamin-C (FLNC). WGS also identified 84 secondary findings (mean=2 per person, range=0-6), which mostly defined carrier status for recessive conditions. CONCLUSIONS:WGS detected nearly all variants identified on panel testing, provided 1 new diagnostic finding, and allowed interrogation of posited disease genes. Several variants of uncertain clinical use and numerous secondary genetic findings were also identified. Whereas panel testing and WGS provided similar diagnostic yield, WGS offers the advantage of reanalysis over time to incorporate advances in knowledge, but requires expertise in genomic interpretation to appropriately incorporate WGS into clinical care. CLINICAL TRIAL REGISTRATION:URL: https://clinicaltrials.gov. Unique identifier: NCT01736566.

Dataset Information

Usefulness of comprehensive targeted multigene panel sequencing for neuromuscular disorders in Korean patients.

Background

Methods

Results

Conclusion

Publications

Usefulness of comprehensive targeted multigene panel sequencing for neuromuscular disorders in Korean patients.

Similar Datasets

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