Limited mutational heterogeneity in the LDLR gene in familial hypercholesterolemia in Tunisia
| Autor: | A.M. Abid, Mathilde Varret, Imen Jguirim, Awatef Jelassi, L. Boughamoura, Mohamed Najah, Jean-Pierre Rabès, Mohamed Naceur Slimane, F. Maatouk, Catherine Boileau, M. Rouis |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Heterozygote Tunisia Adolescent DNA Mutational Analysis Population Nonsense mutation Familial hypercholesterolemia Biology Frameshift mutation Hyperlipoproteinemia Type II Exon medicine Humans Missense mutation education Aged Family Health Genetics education.field_of_study Polymorphism Genetic Autosomal dominant trait Exons medicine.disease Pedigree Receptors LDL Mutation Mutation (genetic algorithm) Female lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine |
| Zdroj: | Atherosclerosis. 203:449-453 |
| ISSN: | 0021-9150 |
| DOI: | 10.1016/j.atherosclerosis.2008.07.011 |
| Popis: | Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the low-density lipoprotein receptor ( LDLR ), apolipoprotein B ( APOB ), and proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) genes. In previous studies, we have identified novel mutations in Tunisian FH families. In this study, we have extended our investigation to additional families. Five unrelated probands were screened for mutations in the LDLR and APOB genes, using direct sequencing and enzymatic restriction. We identified two novel LDLR mutations: a missense mutation in exon 7: p.Gly343Cys (c.1027G>T), and a nonsense mutation in exon 17: p.Lys816X (c.2446A>T). Using the PolyPhen and SIFT prediction computer programs the p.Gly343Cys is predicted to have a deleterious effect on LDL receptor activity. The missense mutation we found in exon 3, p.Cys89Trp (c.267C>G), has previously been identified in patients from United Kingdom and Spain, and is reported here for the first time in the Tunisian population. Finally, the framshift mutation in exon 10, p.Ser493ArgfsX44, is reported here for the fourth and fifth time in Tunisian families. The latter is the most frequent FH-causing mutation in Tunisia. These LDLR gene mutations enrich the spectrum of mutations causing FH in the Tunisian population. The framshift mutation, p.Ser493ArgfsX44, seems to be a founder mutation in this population. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect