| Autor: |
Singh N. Sadananda, Jia Nee Foo, Meng Tiak Toh, Lubomira Cermakova, Laia Trigueros-Motos, Teddy Chan, Herty Liany, Jennifer A. Collins, Sima Gerami, Roshni R. Singaraja, Michael R. Hayden, Gordon A. Francis, Jiri Frohlich, Chiea Chuen Khor, Liam R. Brunham |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Journal of Lipid Research, Vol 56, Iss 10, Pp 1993-2001 (2015) |
| Druh dokumentu: |
article |
| ISSN: |
0022-2275 |
| DOI: |
10.1194/jlr.P058891 |
| Popis: |
A low level of HDL cholesterol (HDL-C) is a common clinical scenario and an important marker for increased cardiovascular risk. Many patients with very low or very high HDL-C have a rare mutation in one of several genes, but identification of the molecular abnormality in patients with extreme HDL-C is rarely performed in clinical practice. We investigated the accuracy and diagnostic yield of a targeted next-generation sequencing (NGS) assay for extreme levels of HDL-C. We developed a targeted NGS panel to capture the exons, intron/exon boundaries, and untranslated regions of 26 genes with highly penetrant effects on plasma lipid levels. We sequenced 141 patients with extreme HDL-C levels and prioritized variants in accordance with medical genetics guidelines. We identified 35 pathogenic and probably pathogenic variants in HDL genes, including 21 novel variants, and performed functional validation on a subset of these. Overall, a molecular diagnosis was established in 35.9% of patients with low HDL-C and 5.2% with high HDL-C, and all prioritized variants identified by NGS were confirmed by Sanger sequencing. Our results suggest that a molecular diagnosis can be identified in a substantial proportion of patients with low HDL-C using targeted NGS. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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