Whole-Exomes Sequencing Delineates Gene Variants Profile in a Young Saudi Male with Familial Hypercholesterolemia: Case Report

Abstract

Familial hypercholesterolemia is an autosomal dominant genetic disease characterized by earlier elevated Low-Density Lipoprotein (LDL) cholesterol levels and increased risk for premature Myocardial Infarction (MI). Albeit the diagnosis of some medical Familial Hypercholesterolemia (FH) cases are due to mutations in PCSK9, APOB, or LDLR, detection of mutation rate and profiles relies heavily on different gene pools and ethnicity. We ran exome sequencing on blood genomic DNA (gDNA) from a 26-year-old Saudi patient on Ion Proton Platform (Ion Torrent, Guilford, Connecticut, USA) as part of a pilot study preluding the establishment of the Saudi Human Genome project. The sequencing results were analysed using Ion suit Bioinformatics system. The patient was matched with a lady of lean body mass and Welsh descent, who suffered from hypercholesterolemia. The first analysis of known FH genes identified five mutations in APOB, 25 mutations of known genes linked to FH, six mutations in LPR2, one mutation in LDLR, and three mutations in PCSK9. Finally, using disease filter algorithms, we filtered out more than 2000 intronic synonymous variants with likely no biological functions. No major new locus was found in FH. However, via variant reduction and TVC protocols we detected 15 new variants, among which 14 genes are linked to hypercholesterolemia, type-I, and type-II diabetes. We also detected three mutations in PCSK9 and confirmed one by Sanger. Taken together, this report suggests that the genetic determinant of FH in this Saudi patient is likely to be heterogeneous, complicating the diagnostic and novel gene discovery process.

Role of Apolipoprotein E gene polymorphism in the risk of familial hypercholesterolemia: a case-control study

“…Genetic susceptibility is thought to contribute to the pathogenesis of FH disease. However, FH prevalence in Saudi Arabia is still not well-documented, with too few studies focused on the subject (Al-Allaf et al, 2017;Al-Allaf et al, 2016;Al-Allaf et al, 2014;Al-Allaf et al, 2015;Alallaf et al, 2017;Alharbi et al, 2013;Alharbi et al, 2015;Nuglozeh, 2017). Moreover, FH disease may have a high prevalence may be due to connection with obesity (68%) and consanguineous marriages (~50-60%) in both the Saudi and Arab populations.…”

Chromosome HeatMap in CDK Patients as Defined by Multiregional Sequencing on Illumina MiSeq Platform

“…Even after running the FASQ data through GATK pipe line followed with variants filtration, diseases association and hard filtration of variants associated with disease [19,20], we still have at least 250 variants per sample remained that will require further subsequent sorting using Bayesian probability and R-algorithm [21], [22]. Since the faulty or variants of interest are usually few, uncovering these mutations from the big number of SNPs or INDELS will necessitate synthesis of a series number of primers that will be used in subsequent Sanger sequencing for final data confirmation [23]. This increases the cost and the load of the labor.…”