Dataset Information

Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia.

ABSTRACT: BACKGROUND: Familial hypercholesterolemia is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor gene. Few and limited analyses of familial hypercholesterolemia have been performed in Malaysia, and the underlying mutations therefore remain largely unknown.We studied a group of 154 unrelated FH patients from a northern area of Malaysia (Kelantan). The promoter region and exons 2-15 of the LDLR gene were screened by denaturing high-performance liquid chromatography to detect short deletions and nucleotide substitutions, and by multiplex ligation-dependent probe amplification to detect large rearrangements. RESULTS: A total of 29 gene sequence variants were reported in 117(76.0%) of the studied subjects. Eight different mutations (1 large rearrangement, 1 short deletion, 5 missense mutations, and 1 splice site mutation), and 21 variants. Eight gene sequence variants were reported for the first time and they were noticed in familial hypercholesterolemic patients, but not in controls (p.Asp100Asp, p.Asp139His, p.Arg471Gly, c.1705+117 T>G, c.1186+41T>A, 1705+112C>G, Dup exon 12 and p.Trp666ProfsX45). The incidence of the p.Arg471Gly variant was 11%. Patients with pathogenic mutations were younger, had significantly higher incidences of cardiovascular disease, xanthomas, and family history of hyperlipidemia, together with significantly higher total cholesterol and low density lipoprotein levels than patients with non-pathogenic variants. CONCLUSIONS: Twenty-nine gene sequence variants occurred among FH patients; those with predicted pathogenicity were associated with higher incidences of cardiovascular diseases, tendon xanthomas, and higher total and low density lipoprotein levels compared to the rest. These results provide preliminary information on the mutation spectrum of this gene among patients with FH in Malaysia.

SUBMITTER: Al-Khateeb A

PROVIDER: S-EPMC3071311 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia.

Al-Khateeb Alyaa A Zahri Mohd K MK Mohamed Mohd S MS Sasongko Teguh H TH Ibrahim Suhairi S Yusof Zurkurnai Z Zilfalil Bin A BA

BMC medical genetics 20110319

<h4>Background</h4>Familial hypercholesterolemia is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor gene. Few and limited analyses of familial hypercholesterolemia have been performed in Malaysia, and the underlying mutations therefore remain largely unknown.We studied a group of 154 unrelated FH patients from a northern area of Malaysia (Kelantan). The promoter region and exons 2-15 of the LDLR gene were screened by denaturing high-performance liquid chromato ...[more]

PMID: 21418584

Similar Datasets

Project description:BACKGROUND: Familial hypercholesterolemia is a human monogenic disease caused by population-specific mutations in the low density lipoprotein (LDL) receptor gene. Despite thirteen different mutations of the LDL receptor gene were reported from Russia prior to 2003, the whole spectrum of disease-causing gene alterations in this country is poorly known and requires further investigation provided by the current study. METHODS: Forty-five patients with clinical diagnosis of FH were tested for the apolipoprotein B (apoB) mutation R3500Q by restriction fragment length analysis. After exclusion of R3500Q mutation high-sensitive fluorescent single-strand conformation polymorphism (SSCP) analysis and automatic DNA sequencing were used to search for mutations in the LDL receptor gene. RESULTS: We found twenty one rare sequence variations of the LDL receptor gene. Nineteen were probably pathogenic mutations, and two (P518P, T705I) were considered as neutral ones. Among the mutations likely to be pathogenic, eight were novel (c.670-671insG, C249X, c.936-940del5, c.1291-1331del41, W422X, c.1855-1856insA, D601N, C646S), and eleven (Q12X, IVS3+1G>A, c.651-653del3, E207X, c.925-931del7, C308Y, L380H, c.1302delG, IVS9+1G>A, V776M, V806I) have already been described in other populations. None of the patients had the R3500Q mutation in the apoB gene. CONCLUSIONS: Nineteen pathogenic mutations in the LDL receptor gene in 23 probands were identified. Two mutations c.925-931del7 and L380H are shared by St.-Petersburg population with neighbouring Finland and several other mutations with Norway, Sweden or Denmark, i.e. countries from the Baltic Sea region. Only four mutations (c.313+1G>A, c.651-653del3, C308Y and W422X) were recurrent as all those were found in two unrelated families. By this study the number of known mutations in the LDL receptor gene in St.-Petersburg area was increased nearly threefold. Analysis of all 34 low density lipoprotein receptor gene mutations found in St.-Petersburg argues against strong founder effect in Russian familial hypercholesterolemia.

Dataset Information

Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia.

Publications

Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets