Screening for genetic mutations in LDLR gene with familial hypercholesterolemia patients in the Saudi population

Alharbi, Khalid Khalaf; Kashour, Tarek; Al-Hussaini, Wejdan; Nbaheen, May Salem; Hasanato, Rana; Mohamed, Sarar; Tamimi, Waleed; Khan, Imran Ali

doi:10.18388/abp.2015_1015

Cited by 21 publications

(12 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, we represented the first description of heterozygous mutations in the exon 4 of the gene for LDLR in Vietnamese patients with hypercholesterolemia. In previous studies, the prevalence of [1,2], made the comparison, in our study, the results showed that 29 cases of 40 cases, counting for 72.5%, which was completely higher. In our initial study, all of 40 clinical samples were collected from FH patients, thus, we initial concluded that the 72.5% FH patients containing the mutation on exon 4 of the LDLR gene.…”

Section: Discussionsupporting

confidence: 59%

Initial study of the mutation in exon 4 of the LDLR gene in Vietnamese patients with Familial hypercholesterolemia

Duc¹,

Huyen²,

Kim³

2016

Sixth International Conference on Advances in Applied Science and Environmental Engineering - ASEE 2016

View full text Add to dashboard Cite

Familial hypercholesterolemia (FH) has been identified as the genetic disorder disease, which is characterized by high total cholesterol, in particularly, the high level of low density lipoprotein (LDL). The normal function of low density lipoprotein receptor is obligate for the normal of lipid profile. The mutation in exon 4 of LDLR gene has been identified to be responsible to FH. In current study, the PCR sequencing method was applied to analyze the mutation of exon 4 of LDLR gene of forty clinical samples, which were diagnosed with FH. As the results, 29 samples of 40 samples, counting for 72.5%. Notably, the genotypes were heterogeneous. In the representative sample DA1, the mutation 355del and c.379G>T (p.V106F) were found, in which, the mutation c.379G>T (p.V106F) has not been previously reported previously. In conclusion, this study being the first comprehensive mutation analysis of the LDLR causing FH in our country. Additionally, mutations identification in exon 4 of LDLR gene is the characteristic of Vietnamese FH patients.

show abstract

Section: Discussionsupporting

confidence: 59%

Initial study of the mutation in exon 4 of the LDLR gene in Vietnamese patients with Familial hypercholesterolemia

Duc¹,

Huyen²,

Kim³

2016

Sixth International Conference on Advances in Applied Science and Environmental Engineering - ASEE 2016

View full text Add to dashboard Cite

show abstract

“…It is interesting to note that FH genetic diagnosis is happening almost all over the world, mainly within the scope of research projects, 30,[32][33][34][35][36][37] since only The Netherlands, Spain, and Uruguay have governmental approval for the identification of FH patients. 38,39 The fact that most variants are restricted to a continent was also an interesting finding, suggesting that population migration occurs mostly within the same continent.…”

Section: Discussionmentioning

confidence: 99%

Analysis of publicly available LDLR, APOB, and PCSK9 variants associated with familial hypercholesterolemia: application of ACMG guidelines and implications for familial hypercholesterolemia diagnosis

Chora

Medeiros

Alves

et al. 2018

Genetics in Medicine

103

View full text Add to dashboard Cite

PurposeFamilial hypercholesterolemia (FH) is an autosomal disorder of lipid metabolism presenting with increased cardiovascular risk. Although more than 1,700 variants have been associated with FH, the great majority have not been functionally proved to affect the low-density lipoprotein receptor cycle. We aimed to classify all described variants associated with FH and to establish the proportion of variants that lack evidence to support their pathogenicity.MethodsWe followed American College of Medical Genetics and Genomics (ACMG) guidelines for the classification, and collected information from a variety of databases and individual reports. A worldwide overview of publicly available FH variants was also performed.ResultsA total of 2,104 unique variants were identified as being associated with FH, but only 166 variants have been proven by complete in vitro functional studies to be causative of disease. Additionally, applying the ACMG guidelines, 1,097 variants were considered pathogenic or likely pathogenic. Only seven variants were found in all five continents.ConclusionThe lack of functional evidence for about 85% of all variants found in FH patients can compromise FH diagnosis and patient prognosis. ACMG classification improves variant interpretation, but functional studies are necessary to understand the effect of about 40% of all variants reported. Nevertheless, ACMG guidelines need to be adapted to FH for a better diagnosis.

show abstract

“…Most prior publications regarding FH patients come from countries that have nationalized health care systems or socialized medicine, offering opportunities to standardize medical practice. 10,16,17 …”

Section: Discussionmentioning

confidence: 99%

US physician practices for diagnosing familial hypercholesterolemia: data from the CASCADE-FH registry

Ahmad

Andersen

et al. 2016

Journal of Clinical Lipidology

View full text Add to dashboard Cite

Background In the US familial hypercholesterolemia (FH), patients are underidentified, despite an estimated prevalence of 1:200 to 1:500. Criteria to identify FH patients include Simon Broome, Dutch Lipid Clinic Network (DLCN), or Make Early Diagnosis to Prevent Early Deaths (MEDPED). The use of these criteria in US clinical practices remains unclear. Objective To characterize the FH diagnostic criteria applied by US lipid specialists participating in the FH Foundation's CASCADE FH (CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia) patient registry. Methods We performed an observational, cross-sectional analysis of diagnostic criteria chosen for each adult patient, both overall and by baseline patient characteristics, at 15 clinical sites that had contributed data to the registry as of September 8, 2015. A sample of 1867 FH adults was analyzed. The median age at FH diagnosis was 50 years, and the median pretreatment low-density lipoprotein cholesterol (LDL-C) value was 238 mg/dL. The main outcome was the diagnostic criteria chosen. Diagnostic criteria were divided into five nonexclusive categories: “clinical diagnosis,” MEDPED, Simon Broome, DLCN, and other. Results Most adults enrolled in CASCADE FH (55.0%) received a “clinical diagnosis.” The most commonly used formal criteria was Simon–Broome only (21%), followed by multiple diagnostic criteria (16%), MEDPED only (7%), DLCN only (1%), and other (0.5%), P < .0001. Of the patients with only a “clinical diagnosis,” 93% would have met criteria for Simon Broome, DLCN, or MEDPED based on the data available in the registry. Conclusions Our findings demonstrate heterogeneity in the application of FH diagnostic criteria in the United States. A nationwide consensus definition may lead to better identification, earlier treatment, and ultimately CHD prevention.

show abstract

Screening for genetic mutations in LDLR gene with familial hypercholesterolemia patients in the Saudi population

Cited by 21 publications

References 15 publications

Initial study of the mutation in exon 4 of the LDLR gene in Vietnamese patients with Familial hypercholesterolemia

Initial study of the mutation in exon 4 of the LDLR gene in Vietnamese patients with Familial hypercholesterolemia

Analysis of publicly available LDLR, APOB, and PCSK9 variants associated with familial hypercholesterolemia: application of ACMG guidelines and implications for familial hypercholesterolemia diagnosis

US physician practices for diagnosing familial hypercholesterolemia: data from the CASCADE-FH registry

Contact Info

Product

Resources

About