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- Title
Accurate genetic diagnosis of Finnish pulmonary arterial hypertension patients using oligonucleotide-selective sequencing.
- Authors
Vattulainen, Sanna; Aho, Joonas; Salmenperä, Pertteli; Bruce, Siina; Tallila, Jonna; Gentile, Massimiliano; Sankelo, Marja; Laitinen, Tarja; Koskenvuo, Juha W.; Alastalo, Tero‐Pekka; Myllykangas, Samuel
- Abstract
The genetic basis of pulmonary arterial hypertension ( PAH) among Finnish PAH patients is poorly understood. We adopted a novel-targeted next-generation sequencing ( NGS) approach called Oligonucleotide-Selective Sequencing ( OS-Seq) and developed a custom data analysis and interpretation pipeline to identify pathogenic base substitutions, insertions, and deletions in seven genes associated with PAH ( BMPR2, BMPR1B, ACVRL1, ENG, SMAD9, CAV1, and KCNK3) from Finnish PAH patients. 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.
- Subjects
HYPERTENSION; OLIGONUCLEOTIDES; GENETIC mutation; CLINICAL medicine; DIAGNOSTIC examinations
- Publication
Molecular Genetics & Genomic Medicine, 2015, Vol 3, Issue 4, p354
- ISSN
2324-9269
- Publication type
Article
- DOI
10.1002/mgg3.147