Screening of LDLR and APOB gene mutations in Mexican patients with homozygous familial hypercholesterolemia
| Autor: | César Augusto Zarate Morales, Juan Ramón González García, Ana Gabriela Colima Fausto, Norma Alejandra Vázquez Cárdenas, María Teresa Magaña Torres, Teresita De Jesús Hernández Flores, Yoaly Josefina Sánchez López |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male Apolipoprotein B Adolescent Endocrinology Diabetes and Metabolism Familial hypercholesterolemia 030204 cardiovascular system & hematology medicine.disease_cause Hyperlipoproteinemia Type II 03 medical and health sciences symbols.namesake Young Adult 0302 clinical medicine Internal Medicine Medicine Humans Computer Simulation Allele Child Gene Mexico Apolipoproteins B Sanger sequencing Genetics Mutation Nutrition and Dietetics biology business.industry Homozygote medicine.disease Phenotype Pedigree 030104 developmental biology Receptors LDL Child Preschool LDL receptor biology.protein symbols lipids (amino acids peptides and proteins) Female Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of clinical lipidology. 12(3) |
| ISSN: | 1933-2874 |
| Popis: | Background Familial hypercholesterolemia (FH) is an autosomal dominant disorder that causes accumulation of serum low-density lipoprotein cholesterol and premature cardiovascular disease. It is mainly related to mutations in the LDLR gene. Homozygous FH (HoFH) patients have the most severe form of the disease accounting for a worldwide prevalence of 1:1,000,000. In Mexico, at least 5 cases of HoFH have been reported. Objective The aim of this study was to describe the clinical, biochemical, and molecular data observed in patients with HoFH phenotype. Methods We included 13 patients, belonging to 11 families, with clinical and biochemical diagnoses suggestive of HoFH. Molecular analyses of the LDLR and APOB genes were performed by means of polymerase chain reaction followed by Sanger sequencing. Results The causal mutation of HoFH was found in 8 of 11 unrelated patients. Excepting 1, all were true homozygotes. Six different variants in LDLR were identified: c.-139delCTCCCCCTGC, p.Glu140Lys, p.Asp360His, p.Asn405Lys, p.Ala755Glyfs*7, and p.Leu759Serfs*6. Of these, p.Asp360His and p.Asn405Lys were detected for the first time in Mexico; p.Leu759Serfs*6 showed to be the most frequent (43.7% of the alleles 7/16), and c.-139delCTCCCCCTGC is a new variant located in the promoter region. Conclusions This work increases knowledge of biochemical and genetic features in Mexican patients with HoFH. A novel mutation in the LDLR gene promoter was detected: c.-139delCTCCCCCTGC, which possibly inhibits its expression. |
| Databáze: | OpenAIRE |
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