Autosomal Dominant Hypercholesterolemia (ADH) is a heterogeneous common disorder characterized by elevated levels of plasma low-density lipoprotein (LDL-C), total cholesterol, and increased risk of cardiovascular disease. Uncovering the molecular determinants that underlie ADH is a major focus of cardiovascular research, but despite rapid technical advances, efforts to identify novel ADH genes have yet not been very successful.
Commonly used noveI-gene-finding criteria are LDL-C levels above the 95th percentile and a disease penetrance of 0.9. However, by applying such criteria the phenotypic and genetic heterogeneity of ADH will be largely ignored.
Our findings clearly showed that adjusted and refined phenotypic definitions within ADH families are necessary to increase the change of identifying novel genes associated with the ADH phenotype, and using a cut-point at the 75th percentile seems to be justified. (By Dr. Sigrid Fouchier, http://jmg.bmj.com/content/early/2014/11/20/jmedgenet-2014-102653 )