Comprehensive Diagnostic Testing for Stereocilin: An Approach for Analyzing Medically Important Genes with High Homology

摘要: Next-generation sequencing (NGS) technologies have revolutionized genetic testing by enabling simultaneous analysis of unprecedented numbers genes. However, genes with high-sequence homology pose challenges to current NGS technologies. Because diagnostic is moving toward exome analysis, knowledge these homologous essential avoid false positive and negative results. An example the STRC gene, one >70 known contribute basis hearing loss. 99.6% identical a pseudogene (pSTRC) therefore inaccessible standard methodologies. The locus also be common site for large deletions. Comprehensive inherited loss necessitates combination several approaches interference. We developed clinical test that combines NGS-based copy number assessment supplemented long-range PCR-based Sanger or MiSeq assay eliminate contamination. By using this assays we could identify biallelic variants in 14% (95% CI, 8%–24%) individuals isolated nonsyndromic who had previously tested on our 70-gene panel, corresponding detection rate 11.2% 6%–19%) untested patients. This approach has broad applicability because medically significant many disease areas include homology.