Comparison of the genetic defect with LDL-receptor activity in cultured cells from patients with a clinical diagnosis of heterozygous familial hypercholesterolemia. The Familial Hypercholesterolaemia Regression Study Group
| Autor: | X M, Sun, D D, Patel, B L, Knight, A K, Soutar |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Adult
Male Heterozygote DNA Mutational Analysis Middle Aged Polymerase Chain Reaction Linkage Disequilibrium Pedigree Hyperlipoproteinemia Type II Lipoproteins LDL Genetic Heterogeneity Phenotype Receptors LDL Humans Female Lymphocytes RNA Messenger Deoxyribonucleases Type II Site-Specific Chromosomes Human Pair 19 Cells Cultured Polymorphism Restriction Fragment Length Polymorphism Single-Stranded Conformational Apolipoproteins B Sequence Deletion |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 17(11) |
| ISSN: | 1079-5642 |
| Popis: | In this study we have analyzed the genetic defect in 42 patients with a diagnosis of heterozygous familial hypercholesterolemia (FH) by Southern blotting, SSCP, and sequencing of PCR-amplified fragments of genomic DNA or sequencing of RT-PCR products from mRNA in cultured cells. The apoB Arg3500Gln mutation was identified in five patients. A molecular defect in the LDL-receptor gene was confirmed in 23 patients; 16 of these mutations have not been described before. No defect in the coding region, intron:exon junctions or proximal promoter of the LDL-receptor gene or in the region of the apoB gene coding for the LDL-receptor binding domain was found in the remaining 14 patients. LDL-receptor activity and protein content of cultured lymphoblasts from the patients was significantly lower in cells from patients with severe rather than mild LDL-receptor mutations. Cells from four patients with no detectable defect showed reduced LDL receptor activity compared with eight normal cell lines, whereas six others had reduced LDL-receptor activity but LDL-receptor protein content within the normal range. Cells from four patients appeared to have normal LDL-receptor function. Cells from two patients with a defined defect also had LDL-receptor activity within the normal range. The findings demonstrate the problems involved in the genetic diagnosis of FH in patients. |
| Databáze: | OpenAIRE |
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