[Familial hypercholesterolemia: molecular identification and characterization of the first compound homozygote in...

Homozygous familial hypercholestrolemia (FH) is a rare genetic disorder (one in 1 million persons) due to two different mutations in the LDL receptor gene (compound homozygous) or, rarely, to the presence of the same mutation in the two aleles. In these patients the absence of a functional LDL receptor produces extreme elevations of plasma cholesterol levels that need an aggressive and expensive treatment with LDL apheresis or hepatic transplantation. The clinical evolution is poor with early coronary heart disease. Molecular biology techniques allow a genetic diagnosis and a genetic counseling in the affected subjects. We have identified and characterized the first compound homozygous of FH in Spain using the single strand conformational polymorphism (SSCP) analysis. The patient is a 30 years old female, who carried two different mutations in the LDL receptor gene: the G528V and the D280G (a new mutation). These mutations produce significant changes in the aminoacid sequence and could be classified as class 2.