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Updated: Jul 14, 2026
Genetic Variant Detection in the CALR gene using High Resolution Melting Analysis
Published on: August 26, 2020
Integrated analysis of STRC variants in hereditary hearing impairment using maker-mediated refinement of long-read
Cheng-Yu Tsai1,2, Yue-Sheng Lu1, Yu-Ting Chiang2
1Department of Otolaryngology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100225, Taiwan.
Background:
Sensorineural hearing impairment (SNHI) is a common disorder with a significant genetic basis. Standard next-generation sequencing (NGS) often fails to accurately identify pathogenic variants in the STRC gene due to its complex genomic structure, including large rearrangements and a highly homologous pseudogene. Long-read sequencing (LRS) offers improved resolution for these complex regions.
Methods:
We developed a comprehensive workflow that integrates PacBio-based LRS with marker-mediated refinements and MLPA validations to specifically address pseudogene interference. This methodology was applied to analyze the STRC gene in a cohort of 100 unrelated Taiwanese patients with SNHI of unknown genetic origin after initial NGS screening.
Results:
We identified bi-allelic STRC variants in 11 unrelated patients (11% diagnostic yield), including homozygous deletions, compound heterozygous deletions and conversions, and compound heterozygous single nucleotide variants (SNVs) and copy number variants (CNVs). All unrelated cases resolved with bi-allelic STRC variants were affected with mild or moderate SNHI, occupying 15.1% of total 73 mild-to-moderate SNHI patients in this study.
Conclusion:
Our results highlight the diagnostic utility of this combined strategy, integrating LRS with marker-mediated refinements that validated by MLPA assays, in detecting complex STRC variants and advance the understanding of the genetic etiology of SNHI that remains unresolved by conventional NGS approaches.
