Vinje_2018_Mol.Genet.Metab_123_169

Reference

Title : Prevalence of cholesteryl ester storage disease among hypercholesterolemic subjects and functional characterization of mutations in the lysosomal acid lipase gene - Vinje_2018_Mol.Genet.Metab_123_169
Author(s) : Vinje T , Wierod L , Leren TP , Strom TB
Ref : Mol Genet Metab , 123 :169 , 2018
Abstract :

Lysosomal acid lipase hydrolyzes cholesteryl esters and triglycerides contained in low density lipoprotein. Patients who are homozygous or compound heterozygous for mutations in the lysosomal acid lipase gene (LIPA), and have some residual enzymatic activity, have cholesteryl ester storage disease. One of the clinical features of this disease is hypercholesterolemia. Thus, patients with hypercholesterolemia who do not carry a mutation as a cause of autosomal dominant hypercholesterolemia, may actually have cholesteryl ester storage disease. In this study we have performed DNA sequencing of LIPA in 3027 hypercholesterolemic patients who did not carry a mutation as a cause of autosomal dominant hypercholesterolemia. Functional analyses of possibly pathogenic mutations and of all mutations in LIPA listed in The Human Genome Mutation Database were performed to determine the pathogenicity of these mutations. For these studies, HeLa T-REx cells were transiently transfected with mutant LIPA plasmids and Western blot analysis of cell lysates was performed to determine if the mutants were synthesized in a normal fashion. The enzymatic activity of the mutants was determined in lysates of the transfected cells using 4-methylumbelliferone-palmitate as the substrate. A total of 41 mutations in LIPA were studied, of which 32 mutations were considered pathogenic by having an enzymatic activity <10% of normal. However, none of the 3027 hypercholesterolemic patients were homozygous or compound heterozygous for a pathogenic mutation. Thus, cholesteryl ester storage disease must be a very rare cause of hypercholesterolemia in Norway.

PubMedSearch : Vinje_2018_Mol.Genet.Metab_123_169
PubMedID: 29196158
Gene_locus related to this paper: human-LIPA

Related information

Mutation L264P_human-LIPA    Q85K_human-LIPA    N98K_human-LIPA    G342W_human-LIPA    G342R_human-LIPA    Q298H_human-LIPA    T288I_human-LIPA    Q85R_human-LIPA    Q87V_human-LIPA    W95R_human-LIPA    R127W_human-LIPA    D145E_human-LIPA    P202L_human-LIPA    R276K_human-LIPA    I391S_human-LIPA    L294S_human-LIPA    H295Y_human-LIPA    L357P_human-LIPA    S289C_human-LIPA    N119S_human-LIPA    H129P_human-LIPA    H129R_human-LIPA    L200P_human-LIPA
Gene_locus L264P_human-LIPA    Q85K_human-LIPA    N98K_human-LIPA    G342W_human-LIPA    G342R_human-LIPA    Q298H_human-LIPA    T288I_human-LIPA    Q85R_human-LIPA    Q87V_human-LIPA    W95R_human-LIPA    R127W_human-LIPA    D145E_human-LIPA    P202L_human-LIPA    R276K_human-LIPA    I391S_human-LIPA    L294S_human-LIPA    H295Y_human-LIPA    L357P_human-LIPA    S289C_human-LIPA    N119S_human-LIPA    H129P_human-LIPA    H129R_human-LIPA    L200P_human-LIPA    human-LIPA
Disease L264P_human-LIPA    Q85K_human-LIPA    N98K_human-LIPA    G342W_human-LIPA    G342R_human-LIPA    Q298H_human-LIPA    T288I_human-LIPA    Q85R_human-LIPA    Q87V_human-LIPA    W95R_human-LIPA    R127W_human-LIPA    D145E_human-LIPA    P202L_human-LIPA    R276K_human-LIPA    I391S_human-LIPA    L294S_human-LIPA    H295Y_human-LIPA    L357P_human-LIPA    S289C_human-LIPA    N119S_human-LIPA    H129P_human-LIPA    H129R_human-LIPA    L200P_human-LIPA    human-LIPA    Wolman disease WD, Cholesterol Ester Storage Disease, CESD

Citations formats

Vinje T, Wierod L, Leren TP, Strom TB (2018)
Prevalence of cholesteryl ester storage disease among hypercholesterolemic subjects and functional characterization of mutations in the lysosomal acid lipase gene
Mol Genet Metab 123 :169

Vinje T, Wierod L, Leren TP, Strom TB (2018)
Mol Genet Metab 123 :169