Whole-Exomes Sequencing Delineates Gene Variants Profile in a Young Saudi Male with Familial Hypercholesterolemia: Case Report.
PMID 28764195 | PMCID PMC5535388 | DOI 10.7860/JCDR/2017/28156.10143 · Journal of clinical and diagnostic research : JCDR · 2017
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.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | PCSK9 | “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.” | 0.98 | hgnc_dict_v1 |
| gene | APOB | “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.” | 0.98 | hgnc_dict_v1 |
| gene | LDLR | “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.” | 0.98 | hgnc_dict_v1 |
| phenotype | familial hypercholesterolemia | “Whole-Exomes Sequencing Delineates Gene Variants Profile in a Young Saudi Male with Familial Hypercholesterolemia: Case Report.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | myocardial infarction | “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).” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | diabetes mellitus | “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.” | 0.93 | phenotype_alias_lexicon_v2 |
| population | Saudi Arabia | “Whole-Exomes Sequencing Delineates Gene Variants Profile in a Young Saudi Male with Familial Hypercholesterolemia: Case Report. 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. 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.” | 0.95 | saudi_context_rules_v1 |