Please use this identifier to cite or link to this item: https://doi.org/10.1186/s12944-018-0763-z
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dc.titleSpectrum of low-density lipoprotein receptor (LDLR) mutations in a cohort of Sri Lankan patients with familial hypercholesterolemia - A preliminary report
dc.contributor.authorPaththinige, C.S
dc.contributor.authorRajapakse, J.R.D.K
dc.contributor.authorConstantine, G.R
dc.contributor.authorSem, K.P
dc.contributor.authorSingaraja, R.R
dc.contributor.authorJayasekara, R.W
dc.contributor.authorDissanayake, V.H.W
dc.date.accessioned2020-09-09T10:07:36Z
dc.date.available2020-09-09T10:07:36Z
dc.date.issued2018
dc.identifier.citationPaththinige, C.S, Rajapakse, J.R.D.K, Constantine, G.R, Sem, K.P, Singaraja, R.R, Jayasekara, R.W, Dissanayake, V.H.W (2018). Spectrum of low-density lipoprotein receptor (LDLR) mutations in a cohort of Sri Lankan patients with familial hypercholesterolemia - A preliminary report. Lipids in Health and Disease 17 (1) : 100. ScholarBank@NUS Repository. https://doi.org/10.1186/s12944-018-0763-z
dc.identifier.issn1476-511X
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/175387
dc.description.abstractBackground: Hypercholesterolemia is a major determinant of cardiovascular disease-associated morbidity and mortality. Mutations in the LDL-receptor (LDLR) gene are implicated in the majority of the cases with familial hypercholesterolemia (FH). However, the spectrum of mutations in the LDLR gene in Sri Lankan patients has not been investigated. The objective of this study was to report the frequency and spectrum of variants in LDLR in a cohort of Sri Lankan patients with FH. Methods: A series of consecutive patients with FH, diagnosed according to Modified Simon Broome criteria or Dutch Lipid Clinic Network criteria at the University Medical Unit, Colombo, were recruited. Clinical data was recorded. DNA was extracted from peripheral blood samples. The LDLR gene was screened for genetic variants by Sanger sequencing. Results: A total of 27 patients [13 (48%) males, 14 (52%) females; age range 24-73 years] were tested. Clinical features found among these 27 patients were: xanthelasma in 5 (18.5%), corneal arcus in 1 (3.7%), coronary artery disease (CAD) in 10 (37%), and a family history of hypercholesterolemia and/or CAD in 24 (88.9%) patients. In the entire cohort, mean total cholesterol was 356.8 mg/dl (±66.4) and mean LDL-cholesterol was 250.3 mg/dl (±67.7). Sanger sequencing of the 27 patients resulted in the identification of known pathogenic missense mutations in 5 (18.5%) patients. Four were heterozygotes for 1 mutation each. They were c.682G > C in 2 patients, c.1720C > A in 1 patient, and c.1855 T > A in 1 patient. One patient with severe FH phenotypes was a compound heterozygote for one known mutation, c.2289G > T, and another missense variant, c.1670C > G (p.Thr557Ser), with unknown functional impact. This latter variant has not been reported in any other population previously. Conclusions: The frequency of known mutations in the LDLR gene in this cohort of patients was markedly low compared to frequencies reported in other populations. This highlights the likelihood of a complex, polygenic inheritance of FH in Sri Lankan patients, indicating the need for a comprehensive genetic evaluation that includes the screening for mutations in other genes that cause FH, such as APOB, PCSK9, and LDLRAP1. © 2018 The Author(s).
dc.sourceUnpaywall 20200831
dc.subjectDNA
dc.subjectlow density lipoprotein cholesterol
dc.subjectlow density lipoprotein receptor
dc.subjectLDLR protein, human
dc.subjectlow density lipoprotein cholesterol
dc.subjectlow density lipoprotein receptor
dc.subjectadult
dc.subjectaged
dc.subjectArticle
dc.subjectblood sampling
dc.subjectclinical article
dc.subjectclinical feature
dc.subjectcohort analysis
dc.subjectcornea curvature
dc.subjectcoronary artery disease
dc.subjectdisease classification
dc.subjectdisease severity
dc.subjectDNA extraction
dc.subjectfamilial hypercholesterolemia
dc.subjectfamily history
dc.subjectfemale
dc.subjectgene frequency
dc.subjectgenetic variability
dc.subjectheterozygote
dc.subjecthuman
dc.subjecthypercholesterolemia
dc.subjectLDLR gene
dc.subjectlow density lipoprotein cholesterol level
dc.subjectmale
dc.subjectmissense mutation
dc.subjectModified Simon Broome criteria
dc.subjectphenotype
dc.subjectSanger sequencing
dc.subjectSri Lankan
dc.subjectxanthelasma
dc.subjectcoronary artery disease
dc.subjectgenetics
dc.subjectheterozygote
dc.subjecthypercholesterolemia
dc.subjectmiddle aged
dc.subjectmutation
dc.subjectpathology
dc.subjectSri Lanka
dc.subjectAdult
dc.subjectAged
dc.subjectCholesterol, LDL
dc.subjectCoronary Artery Disease
dc.subjectFemale
dc.subjectHeterozygote
dc.subjectHumans
dc.subjectHypercholesterolemia
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectMutation
dc.subjectPhenotype
dc.subjectReceptors, LDL
dc.subjectSri Lanka
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.contributor.departmentMEDICINE
dc.description.doi10.1186/s12944-018-0763-z
dc.description.sourcetitleLipids in Health and Disease
dc.description.volume17
dc.description.issue1
dc.description.page100
dc.published.statePublished
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