Detection of familial hypercholesterolemia in a cohort of children with hypercholesterolemia: results of a family and DNA-based screening
| Autor: | Alfredo Cantafora, Francesco Martino, Anna Montali, R. Antonini, Filomena Campagna, Eliana Martino, Maura Bifolco, Marcello Arca, Roberto Verna, Francesco Morrone |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Adolescent Familial hypercholesterolemia Polymorphism Single Nucleotide Cohort Studies Hyperlipoproteinemia Type II chemistry.chemical_compound children Reference Values Internal medicine Hyperlipidemia medicine hyperlipidemia Humans Mass Screening genetics Genetic Testing Allele ldl receptor gene Child familial hypercholesterolemia Vascular disease Cholesterol business.industry Cholesterol LDL medicine.disease Endocrinology El Niño chemistry Italy Receptors LDL Child Preschool Cohort LDL receptor Female Cardiology and Cardiovascular Medicine business Biomarkers |
| Zdroj: | Atherosclerosis. 196(1) |
| ISSN: | 1879-1484 |
| Popis: | The diagnosis of familial hypercholesterolemia (FH) in unselected children is difficult due to the frequent overlap of cholesterol values in affected and non-affected and the paucity of physical signs. Nevertheless, detection and treatment of FH in childhood has been advocated to prevent atherosclerosis in these patients. Here, we report the results of a screening program in a cohort of 157 unrelated, hypercholesterolemic (HC) children (age range 2-15 years; mean 8.3+/-3.4 years) carried out by a combination of family study and molecular analysis of the LDLR gene. On the basis of the familial phenotype, 27 (17.2%) were classified as probable FH and 49 (31.2%) as affected by FCHL. Among probable FH children, 14 (51.8%) carried mutant LDLR alleles, giving an overall 8.9% prevalence of FH. Most of LDLR variants were already reported, but three new mutations G266C, T368M, and D451Y were identified. Beside increased TC and LDL-C (p0.001), FH children showed decreased HDL-C (p0.05) and higher prevalence of family history of CAD when compared to non-FH children. None presented tendon xanthomas. We estimated that LDL-C3.9 mmol/L was the best cut off value for diagnosing FH in these children, showing 79% sensitivity and 71.0% specificity. We propose the use of a LDL-C cut off level associated with a family study to identify FH among HC children. |
| Databáze: | OpenAIRE |
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