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Single, short in‐del, and copy number variations detection in monogenic dyslipidemia using a next‐generation sequencing strategy
Author(s) -
Marmontel O.,
Charrière S.,
Simonet T.,
Bonnet V.,
Dumont S.,
Mahl M.,
Jacobs C.,
y S.,
Chabane K.,
Bozon D.,
Janin A.,
Peretti N.,
Lachaux A.,
Bardel C.,
Millat G.,
Moulin P.,
Marçais C.,
Di Filippo M.
Publication year - 2018
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13250
Subject(s) - dyslipidemia , hypertriglyceridemia , pcsk9 , dna sequencing , copy number variation , computational biology , genetics , medicine , bioinformatics , biology , gene , lipoprotein , ldl receptor , genome , triglyceride , cholesterol , obesity
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.