Spectrum of low-density lipoprotein receptor (LDLR) mutations in a cohort of Sri Lankan patients with familial hypercholesterolemia - a preliminary report.
| Title: | Spectrum of low-density lipoprotein receptor (LDLR) mutations in a cohort of Sri Lankan patients with familial hypercholesterolemia - a preliminary report. |
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| Authors: | Paththinige CS; Human Genetics Unit, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo, 00800, Sri Lanka. paththinige@yahoo.com.; Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Anuradhapura, Sri Lanka. paththinige@yahoo.com.; Rajapakse JRDK; Human Genetics Unit, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo, 00800, Sri Lanka.; Constantine GR; Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.; Sem KP; Translational Laboratory in Genetic Medicine, Agency for Science Technology and Research, National University of Singapore, Singapore, Singapore.; Singaraja RR; Translational Laboratory in Genetic Medicine, Agency for Science Technology and Research, National University of Singapore, Singapore, Singapore.; Jayasekara RW; Human Genetics Unit, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo, 00800, Sri Lanka.; Dissanayake VHW; Human Genetics Unit, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo, 00800, Sri Lanka. |
| Source: | Lipids in health and disease [Lipids Health Dis] 2018 May 02; Vol. 17 (1), pp. 100. Date of Electronic Publication: 2018 May 02. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: BioMed Central Country of Publication: England NLM ID: 101147696 Publication Model: Electronic Cited Medium: Internet ISSN: 1476-511X (Electronic) Linking ISSN: 1476511X NLM ISO Abbreviation: Lipids Health Dis Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : BioMed Central, 2002- |
| MeSH Terms: | Cholesterol, LDL/*genetics ; Coronary Artery Disease/*genetics ; Hypercholesterolemia/*genetics ; Receptors, LDL/*genetics; Coronary Artery Disease/epidemiology ; Coronary Artery Disease/pathology ; Hypercholesterolemia/epidemiology ; Hypercholesterolemia/pathology ; Sri Lanka/epidemiology ; Adult ; Aged ; Female ; Heterozygote ; Humans ; Male ; Middle Aged ; Mutation ; Phenotype |
| 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. |
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| Contributed Indexing: | Keywords: Familial hypercholesterolemia; LDLR gene; Single nucleotide variants (SNV) |
| Substance Nomenclature: | 0 (Cholesterol, LDL); 0 (LDLR protein, human); 0 (Receptors, LDL) |
| Entry Date(s): | Date Created: 20180504 Date Completed: 20180919 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC5932885 |
| DOI: | 10.1186/s12944-018-0763-z |
| PMID: | 29720182 |
| Database: | MEDLINE |
Journal Article