A novel splice site mutation of the LDL receptor gene in a Tunisian hypercholesterolemic family.
Clin Chim Acta
; 392(1-2): 25-9, 2008 Jun.
Article
em En
| MEDLINE
| ID: mdl-18355452
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas B
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Receptores de LDL
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Sítios de Splice de RNA
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Fibroblastos
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Hipercolesterolemia
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Mutação
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article