Mutational analysis of the LDL receptor and APOB genes in Mexican individuals with autosomal dominant hypercholesterolemia
| Autor: | María Teresa Magaña, Ingrid P. Dávalos, Vaca G, Bertha Marìn, Gabriela Carrillo, Esperanza Pérez Martínez, María Lourdes Ramirez, Alejandra Vàzquez |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Proband Adolescent Genotype Apolipoprotein B DNA Mutational Analysis Familial hypercholesterolemia Compound heterozygosity medicine.disease_cause Hyperlipoproteinemia Type II medicine Humans Allele Mexico Alleles Aged Apolipoproteins B Genetics Mutation biology Anticholesteremic Agents PCSK9 Homozygote Sequence Analysis DNA Middle Aged medicine.disease Cholesterol Phenotype Receptors LDL biology.protein Female lipids (amino acids peptides and proteins) Allelic heterogeneity Cardiology and Cardiovascular Medicine |
| Zdroj: | Atherosclerosis. 218:391-396 |
| ISSN: | 0021-9150 |
| DOI: | 10.1016/j.atherosclerosis.2011.06.006 |
| Popis: | The goal of this project was to identify families with autosomal dominant hypercholesterolemia (ADH) to facilitate early detection and treatment and to provide genetic counselling as well as to approximate the mutational diversity of ADH in Mexico. Mutational analysis of the LDLR and APOB genes in 62 index cases with a clinical and/or biochemical diagnosis of ADH was performed. Twenty-five mutations (24 LDLR , 1 APOB ) were identified in 38 index cases. A total of 162 individuals with ADH were identified using familial segregation analysis performed in 269 relatives of the index cases. In addition, a novel PCSK9 mutation, c.1850 C>A (p.Ala617Asp), was detected. The LDLR mutations showed the following characteristics: (1) four mutations are novel: c.695 −1G>T, c.1034_1035insA, c.1586 G>A, c.2264_2273del; (2) the most common mutations were c.682 G>A (FH-Mexico), c.1055 G>A (FH-Mexico 2), and c.1090 T>C (FH-Mexico 3); (3) five mutations were identified in 3 or more apparently unrelated probands; (4) three mutations were observed in a true homozygous state; and (5) four index cases were compound heterozygous, and one was a carrier of two mutations in the same allele. These results suggest that, in Mexico, ADH exhibits allelic heterogeneity with 5 relatively common LDLR mutations and that mutations in the APOB gene are not a common cause of ADH. This knowledge is important for the genotype–phenotype correlation and for optimising both cholesterol lowering therapies and mutational analysis protocols. In addition, these data contribute to the understanding of the molecular basis of ADH in Mexico. |
| Databáze: | OpenAIRE |
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