Dataset Information

Identification of gene mutations in patients with primary periodic paralysis using targeted next-generation sequencing.

ABSTRACT:

Background

Primary periodic paralysis is characterized by recurrent quadriplegia typically associated with abnormal serum potassium levels. The molecular diagnosis of primary PP previously based on Sanger sequencing of hot spots or exon-by-exon screening of the reported genes.

Methods

We developed a gene panel that includes 10 ion channel-related genes and 245 muscular dystrophy- and myopathy-related genes and used this panel to diagnose 60 patients with primary periodic paralysis and identify the disease-causing or risk-associated gene mutations.

Results

Mutations of 5 genes were discovered in 39 patients (65.0%). SCN4A, KCNJ2 and CACNA1S variants accounted for 92.5% of the patients with a genetic diagnosis.

Conclusions

Targeted next-generation sequencing offers a cost-effective approach to expand the genotypes of primary periodic paralysis. A clearer genetic profile enables the prevention of paralysis attacks, avoidance of triggers and the monitoring of complications.

SUBMITTER: Luo S

PROVIDER: S-EPMC6505267 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Identification of gene mutations in patients with primary periodic paralysis using targeted next-generation sequencing.

Luo Sushan S Xu Minjie M Sun Jian J Qiao Kai K Song Jie J Cai Shuang S Zhu Wenhua W Zhou Lei L Xi Jianying J Lu Jiahong J Ni Xiaohua X Dou Tonghai T Zhao Chongbo C

BMC neurology 20190508 1

<h4>Background</h4>Primary periodic paralysis is characterized by recurrent quadriplegia typically associated with abnormal serum potassium levels. The molecular diagnosis of primary PP previously based on Sanger sequencing of hot spots or exon-by-exon screening of the reported genes.<h4>Methods</h4>We developed a gene panel that includes 10 ion channel-related genes and 245 muscular dystrophy- and myopathy-related genes and used this panel to diagnose 60 patients with primary periodic paralysis ...[more]

PMID: 31068157

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Project description:BackgroundWith the expanded availability of next generation sequencing (NGS)-based clinical genetic tests, clinicians seeking to test patients with Mendelian diseases must weigh the superior coverage of targeted gene panels with the greater number of genes included in whole exome sequencing (WES) when considering their first-tier testing approach. Here, we use an in silico analysis to predict the analytic sensitivity of WES using pathogenic variants identified on targeted NGS panels as a reference.MethodsCorresponding nucleotide positions for 1533 different alterations classified as pathogenic or likely pathogenic identified on targeted NGS multi-gene panel tests in our laboratory were interrogated in data from 100 randomly-selected clinical WES samples to quantify the sequence coverage at each position. Pathogenic variants represented 91 genes implicated in hereditary cancer, X-linked intellectual disability, primary ciliary dyskinesia, Marfan syndrome/aortic aneurysms, cardiomyopathies and arrhythmias.ResultsWhen assessing coverage among 100 individual WES samples for each pathogenic variant (153,300 individual assessments), 99.7% (n = 152,798) would likely have been detected on WES. All pathogenic variants had at least some coverage on exome sequencing, with a total of 97.3% (n = 1491) detectable across all 100 individuals. For the remaining 42 pathogenic variants, the number of WES samples with adequate coverage ranged from 35 to 99. Factors such as location in GC-rich, repetitive, or homologous regions likely explain why some of these alterations were not detected across all samples. To validate study findings, a similar analysis was performed against coverage data from 60,706 exomes available through the Exome Aggregation Consortium (ExAC). Results from this validation confirmed that 98.6% (91,743,296/93,062,298) of pathogenic variants demonstrated adequate depth for detection.ConclusionsResults from this in silico analysis suggest that exome sequencing may achieve a diagnostic yield similar to panel-based testing for Mendelian diseases.

Dataset Information

Identification of gene mutations in patients with primary periodic paralysis using targeted next-generation sequencing.

Background

Methods

Results

Conclusions

Publications

Identification of gene mutations in patients with primary periodic paralysis using targeted next-generation sequencing.

Similar Datasets

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