Accurate genetic diagnosis of Finnish pulmonary arterial hypertension patients using oligonucleotide‐selective sequencing

This study represents the first clinical study with OS‐Seq technology on patients suffering from a rare genetic disorder. We analyzed DNA samples from 21 Finnish PAH patients, whose BMPR2 and ACVRL1 mutation status had been previously studied using Sanger sequencing. Our sequencing panel covered 100% of the targeted base pairs with >15× sequencing depth. Pathogenic base substitutions were identified in the BMPR2 gene in 29% of the Finnish PAH cases. Two of the pathogenic variant‐positive patients had been previously tested negative using Sanger sequencing. No clinically significant variants were identified in the six other PAH genes. Our study validates the use of targeted OS‐Seq for genetic diagnostics of PAH and revealed pathogenic variants that had been previously missed using Sanger sequencing. The genetic bases of pulmonary arterial hypertension (PAH) are poorly understood among Finnish patients. Utilizing a novel‐targeted next‐generation sequencing approach called Oligonucleotide‐Selective Sequencing (OS‐Seq) we analyzed 21 Finnish patients diagnosed with PAH to detect pathogenic base substitutions, insertions, and deletions in seven genes associated with the disease. Our study presents the first clinical study of Finnish PAH patients using OS‐Seq and validates its use for genetic diagnostics for PAH.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: Original Article Source Type: research