Genotypic and phenotypic characterization of patients with autosomal dominant hypercholesterolemia in sicily

Aim: Autosomal dominant hypercholesterolemia (ADH) is an autosomal dominant disorder characterized by high serum low density lipoproteincholesterol (LDL-C) levels. The clinical manifestations of ADH might vary among affected subjects and the phenotype correlates with the severity of mutation and the specific gene involved. The aim of this study was to evaluate the clinical expression and clinical outcomes in a cohort of ADH subjects. Methods: 300 ADH probands with a DUTCH score > 6 were enrolled in this study and the analysis was extended to the family members of these index cases. Anthropometric measures, clinical and biochemical parameters, life style (smoker and/or alcohol habits) and cardiovascular outcomes were evaluated. A total of 407 relatives were identified and characterized as well. Results: Molecular diagnosis was defined in 62.6 % of probands; 97 % were carriers of pathogenic mutations in LDLR gene (55 different mutations). The phenotypic characterization of LDLR mutation carriers (ADH-1) and revealed that in both sexes independent predictors of the presence of tendon xanthomas were LDL cholesterol, the presence of coronary heart disease (CHD) and of receptor negative mutations. Independent predictors of CHD were male gender, tendon xanthomas. Conclusions: This study confirms the genetic heterogeneity of ADH and underscores that the variability in phenotypic expression of ADH-1 is greatly affected by the type of LDLR mutation.