Sequential sequencing reveals the architecture and complexity of genomic variants in patients with Alport syndrome - PubMed
5 hours ago
- #sequential sequencing
- #Alport syndrome
- #genetic variants
- Alport syndrome (AS) is a prevalent inherited kidney disorder caused by mutations in COL4A3, COL4A4, and COL4A5 genes.
- A sequential sequencing strategy was used in a Chinese cohort of 555 patients, including whole-exome sequencing (WES), whole-genome sequencing (WGS), RNA sequencing (RNA-seq), and nanopore long-read sequencing (NLR-seq).
- 431 distinct variants were identified in 509 (91.7%) patients, with 42.2% being novel.
- Additional sequencing approaches resolved 23 patients with noncoding, copy number, or structural variants.
- Noncoding variants accounted for 16.2% of detected variants and showed ethnic-specific mutagenesis patterns.
- NLR-seq uncovered two novel types of structural variants: large insertions in intronic regions and complex duplication-inversion variants.
- The study provides deeper insights into the genetic architecture of AS and proposes a research paradigm for improving genetic diagnosis of inherited diseases.