[Familial hypercholesterolemia and mutations of the gene for low-density lipoproteins in Italy]. / Ipercolesterolemia familiare e mutazioni nel gene del recettore delle lipoproteine a bassa densità in Italia.

ABSTRACT

The review takes into account molecular bases and major implications for public health in our country of familial hypercholesterolemia (FH) caused by mutations in LDL receptor (LDLR) gene. The relevance of the problem is evidenced by the fact that (a) about 120,000 Italians affected by heterozygous FH face a cardiovascular risk much higher than normal individuals, and (b) their identification is difficult because of the plethora of mutations existing in the country. This report deepens also the relationships between alterations in the coding sequence of LDLR gene and in the function of LDLR protein. Furthermore, it describes, in terms of molecular characteristics and diffusion, the 42 mutations so far detected in Italy that cause about 30% of FH cases. This led us to hypothesize the existence in our country of over hundred different mutations present within defined geographical areas where, in a few cases, they may also have a relatively high incidence (i.e., the so-called FH-clusters). Finally, preliminary studies mentioned here point out the existence of significant correlations between phenotype and genotype of FH and suggest the possibility of realizing on a large scale an early diagnosis and therapy of pathologies caused by a function deficit in LDL receptor.