Authors
Cheng-Yu Tsai, Yue-Sheng Lu, Yu-Ting Chiang, Ming-Yu Lo, Pei-Hsuan Lin, Shih-Feng Tsai, Chuan-Jen Hsu, Pei-Lung Chen, Jacob Shu-Jui Hsu, Chen-Chi Wu
Published in
Molecular medicine (Cambridge, Mass.). Jul 13, 2026. Epub Jul 13, 2026.
Abstract
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.
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.
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.
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.
PMID:
42437880
Bibliographic data and abstract were imported from PubMed on 13 Jul 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 10
- Comments 0