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Single, short in-del, and copy number variations detection in monogenic dyslipidemia using a next-generation sequencing strategy
- Source :
- Clinical Genetics, Clinical Genetics, Wiley, 2018, 94 (1), pp.132-140. ⟨10.1111/cge.13250⟩, Clinical Genetics, 2018, 94 (1), pp.132-140. ⟨10.1111/cge.13250⟩
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- International audience; Optimal molecular diagnosis of primary dyslipidemia is challenging to confirm the diagnosis, test and identify at risk relatives. The aim of this study was to test the application of a single targeted next-generation sequencing (NGS) panel for hypercholesterolemia, hypocholesterolemia, and hypertriglyceridemia molecular diagnosis. NGS workflow based on a custom AmpliSeq panel was designed for sequencing the most prevalent dyslipidemia-causing genes (ANGPTL3, APOA5, APOC2, APOB, GPIHBP1, LDLR, LMF1, LPL, PCSK9) on the Ion PGM Sequencer. One hundred and forty patients without molecular diagnosis were studied. In silico analyses were performed using the NextGENe software and homemade tools for detection of copy number variations (CNV). All mutations were confirmed using appropriate tools. Eighty seven variations and 4 CNV were identified, allowing a molecular diagnosis for 40/116 hypercholesterolemic patients, 5/13 hypocholesterolemic patients, and 2/11, hypertriglyceridemic patients respectively. This workflow allowed the detection of CNV contrary to our previous strategy. Some variations were found in previously unexplored regions providing an added value for genotype-phenotype correlation and familial screening. In conclusion, this new NGS process is an effective mutation detection method and allows better understanding of phenotype. Consequently this assay meets the medical need for individualized diagnosis of dyslipidemia.
- Subjects :
- 0301 basic medicine
genotype phenotype correlation
[SDV]Life Sciences [q-bio]
Comorbidity
monogenic dyslipidemia
Familial hypercholesterolemia
030204 cardiovascular system & hematology
Workflow
autosomal-dominant hypercholesterolemia
0302 clinical medicine
INDEL Mutation
targeted next-generation sequencing
Medicine
Copy-number variation
Child
Genetics (clinical)
Aged, 80 and over
Genetics & Heredity
apo-b gene
familial hypercholesterolemia
copy number variation
Ion torrent PGM
High-Throughput Nucleotide Sequencing
Middle Aged
3. Good health
Child, Preschool
combined hypolipidemia
Adult
Adolescent
DNA Copy Number Variations
ldl-c levels
hypertriglyceridemia
In silico
density-lipoprotein-receptor
Computational biology
apolipoprotein-b
DNA sequencing
Diagnosis, Differential
Young Adult
03 medical and health sciences
lipid disorders
Genetics
Humans
Genetic Predisposition to Disease
Mutation detection
Genetic Testing
Genetic Association Studies
Aged
Dyslipidemias
business.industry
PCSK9
severe
Hypertriglyceridemia
medicine.disease
030104 developmental biology
coronary-heart-disease
business
Biomarkers
Dyslipidemia
Subjects
Details
- ISSN :
- 00099163 and 13990004
- Volume :
- 94
- Database :
- OpenAIRE
- Journal :
- Clinical Genetics
- Accession number :
- edsair.doi.dedup.....fccf2c438b465f6388d2ce19133e012f