LDL Receptor gene mutation in italian children affected by familial hypercholesterolemia.

Background: Familial Hypercholesterolemia (FH) is a genetic disorder of lipid metabolism caused by different mutations of LDL-receptor (LDLR) gene. Aim of this study is to correlate different mutations of LDLR gene in FH children to lipoprotein pattern and family history of cardiovascular disease (CVD). Methods: we have recruited 18 affected (average age 9 3 ys): each subject was analyzed by screening LDLR gene and apolipoprotein (apo) E gene. Lipid profile was tested in all children: total cholesterol (TC), HDL cholesterol and tryglicerides were evaluated with enzymathic method, apo B with immunoturbidimetric method. Family history was investigated with particular attention to CVD in first and second degree relatives. Results: we have identified 12 different mutations of LDLR gene, 5 of which were firstly detected (1075delAGGATC on exon 8; E397X on exon 9; V510I, Y468C and W469R on exon 10). TC, LDL cholesterol (LDLC) and apo B levels range from 352 to 225, 286 to 126, 171 to 91 mg% respectively. Apo E phenotype resulted E3/E3 in 10/14 and E3/E4 in 3/14 children: average LDLC levels were 200 vs 242 mg%. One child presents E2/E3 phenotype and LDLC value which is 47% of the average LDLC levels reported in FH adults affected by the same LDLR gene mutation (135 vs 291 mg%). Family history of CVD resulted positive in 16/18 children and 9/18 reported precocious CVD among their relatives. Conclusions: we observed large variation of lipid levels among children affected by different mutations of LDLR gene. Further studies will be necessary to define the relationship between LDLR mutations, apo E genotype, biochemical profile and cardiovascular risk.