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A novel splice site mutation of the LDL receptor gene in a Tunisian hypercholesterolemic family
- Source :
- Clinica chimica acta; international journal of clinical chemistry. 392(1-2)
- Publication Year :
- 2008
-
Abstract
- Background Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease caused by mutations in either the low-density lipoprotein receptor, the apolipoprotein B or the proprotein convertase subtilisin/kexin type 9 genes. It is characterized by a high concentration of low-density lipoprotein (LDL), which frequently gives rise to premature coronary disease. In this study, we report a novel splice site mutation of the LDL receptor gene in a Tunisian family. Methods Seven patients from the family were screened for mutations in the LDLR gene and the apoB gene, using direct sequencing. RT-PCR and study on cultured skin fibroblast were realised to characterize the effect of novel mutation. Results Direct sequencing of the promoter and 18 exons reveals a G > A substitution in the splice site junction of intron 8 (c.1186 + 1 G > A). Study on cultured skin fibroblasts showed a residual activity of 10% of the LDL receptor. Reverse transcription, amplification and direct sequencing of RNA from patient's lymphocytes reveal a deletion of the final 51 bp of exon 8 preserving the reading frame. Conclusions The study identified a novel splice mutation c.1186 + 1 G > A in the LDL receptor gene. It causes the utilization of a new cryptic donor splice site 51 bp downstream from the normal site.
- Subjects :
- Adult
Male
Tunisia
Apolipoprotein B
LRP1B
Clinical Biochemistry
Hypercholesterolemia
Familial hypercholesterolemia
medicine.disease_cause
Biochemistry
Exon
medicine
Humans
splice
Family
Cells, Cultured
Aged
Apolipoproteins B
Genetics
Mutation
Splice site mutation
biology
Biochemistry (medical)
General Medicine
Fibroblasts
Middle Aged
medicine.disease
Molecular biology
Introns
Receptors, LDL
LDL receptor
biology.protein
lipids (amino acids, peptides, and proteins)
Female
RNA Splice Sites
Subjects
Details
- ISSN :
- 00098981
- Volume :
- 392
- Issue :
- 1-2
- Database :
- OpenAIRE
- Journal :
- Clinica chimica acta; international journal of clinical chemistry
- Accession number :
- edsair.doi.dedup.....84be0c9c1f88094573f7d617928df7bd