Please use this identifier to cite or link to this item: https://doi.org/10.1186/s12944-018-0763-z
Title: Spectrum of low-density lipoprotein receptor (LDLR) mutations in a cohort of Sri Lankan patients with familial hypercholesterolemia - A preliminary report
Authors: Paththinige, C.S
Rajapakse, J.R.D.K
Constantine, G.R
Sem, K.P 
Singaraja, R.R 
Jayasekara, R.W
Dissanayake, V.H.W
Keywords: DNA
low density lipoprotein cholesterol
low density lipoprotein receptor
LDLR protein, human
low density lipoprotein cholesterol
low density lipoprotein receptor
adult
aged
Article
blood sampling
clinical article
clinical feature
cohort analysis
cornea curvature
coronary artery disease
disease classification
disease severity
DNA extraction
familial hypercholesterolemia
family history
female
gene frequency
genetic variability
heterozygote
human
hypercholesterolemia
LDLR gene
low density lipoprotein cholesterol level
male
missense mutation
Modified Simon Broome criteria
phenotype
Sanger sequencing
Sri Lankan
xanthelasma
coronary artery disease
genetics
heterozygote
hypercholesterolemia
middle aged
mutation
pathology
Sri Lanka
Adult
Aged
Cholesterol, LDL
Coronary Artery Disease
Female
Heterozygote
Humans
Hypercholesterolemia
Male
Middle Aged
Mutation
Phenotype
Receptors, LDL
Sri Lanka
Issue Date: 2018
Citation: Paththinige, 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
Abstract: Background: 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).
Source Title: Lipids in Health and Disease
URI: https://scholarbank.nus.edu.sg/handle/10635/175387
ISSN: 1476-511X
DOI: 10.1186/s12944-018-0763-z
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1186_s12944-018-0763-z.pdf1.49 MBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.