BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is commonly caused by mutations in the LDLR, APOB or PCSK9 genes, with untreated mean low density lipoprotein-cholesterol (LDL-C) concentrations being elevated in APOB mutation carriers, even higher in LDLR mutation and highest in those with a PCSK9 mutation. Here we examine this in children with FH from Norway, UK, The Netherlands, Belgium, Czech Republic, Austria, Portugal and Greece. METHODS: Differences in characteristics and pre- and post-treatment lipid concentrations in those with different molecular causes were compared by standard statistical tests. RESULTS: Data were obtained from 2866 children, of whom 2531 (88%) carried a reported LDLR/APOB/PCSK9 variant. In all countries, the most common cause of FH was an LDLR mutation (79% of children, 297 different), but the prevalence of the APOB p.(Arg3527Gln) mutation varied significantly (ranging from 0% in Greece to 39% in Czech Republic, p < 2.2 × 10-16). The prevalence of a family history of premature CHD was significantly higher in children with an LDLR vs APOB mutation (16% vs 7% p=0.0005). Compared to the LDLR mutation group, mean (±SD) concentrations of pre-treatment LDL-C were significantly lower in those with an APOB mutation (n = 2260 vs n = 264, 4.96 (1.08)mmol/l vs 5.88 (1.41)mmol/l, p < 2.2 × 10-16) and lowest in those with a PCSK9 mutation (n = 7, 4.71 (1.22)mmol/l). CONCLUSIONS: The most common cause of FH in children from eight European countries was an LDLR mutation, with the prevalence of the APOB p.(Arg3527Gln) mutation varying significantly across countries. In children, LDLR-FH is associated with higher concentrations of LDL-C and family history of CHD compared to those with APOB-FH.

• Klíčová slova
• Heterozygous familial hypercholesterolaemia, LDL-C concentrations, Mutation spectrum, Statin treatment,
• MeSH
• dítě MeSH
• hyperlipoproteinemie typ II * diagnóza   epidemiologie   genetika   MeSH
• LDL-receptory genetika   MeSH
• lidé MeSH
• lipidy MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 * genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Belgie MeSH
• Česká republika epidemiologie   MeSH
• Evropa MeSH
• Nizozemsko epidemiologie   MeSH
• Norsko MeSH
• Portugalsko MeSH
• Rakousko MeSH
• Řecko MeSH
• Názvy látek
• LDL-receptory MeSH
• lipidy MeSH
• PCSK9 protein, human MeSH Prohlížeč
• proproteinkonvertasa subtilisin/kexin typu 9 * MeSH