Targeted next-generation sequencing to diagnose disorders of HDL cholesterol.
J Lipid Res
; 56(10): 1993-2001, 2015 Oct.
Article
en En
| MEDLINE
| ID: mdl-26255038
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Cardiovasculares
/
Secuenciación de Nucleótidos de Alto Rendimiento
/
Transportador 1 de Casete de Unión a ATP
/
Hipercolesterolemia
/
HDL-Colesterol
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Guideline
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Lipid Res
Año:
2015
Tipo del documento:
Article
País de afiliación:
Singapur