FAMILIAL HYPERCHOLESTEROLEMIA - IDENTIFIC ATION AND MOLECULAR CHARACTERIZATION OF THE FIRST COMPOUND HOMOZYGOUS PATIENT IN SPAIN

Homozygous familiar hypercholesterolemia (FH) is a rare genetic disord er (one in 1 million persons) due to two different mutations in the LD L receptor gene (compound homozygous) or, rarely, to the presence of t he same mutation in the two aleles. In these patients the absence of a functional LDL receptor produces extreme elevations of plasma cholest erol levels that need an aggressive and expensive treatment with LDL a pheresis or hepatic transplantation. The clinical evolution is poor wi th early coronary heart disease. Molecular biology techniques allow a genetic diagnosis and a genetic counseling in the affected subjects. W e have identified and characterized the first compound homozygous ct F H in Spain using the single strand conformational polymorphism (SSCP) analysis, The patient is a 30 years old female, who carried two differ ent mutations in the LDL receptor gene: the G528V and the D280G (a new mutation), These mutations produce significant changes in the aminoac id sequence and could be classified as class 2.