A novel mutation in exon 5 of the low density lipoprotein receptor gene in a Malay family with familial hypercholesterolaemia (FH)

F�amilial hypercholesterolaemia (FH) is an autosomal dominant inherited disease of lipid metabolism caused by mutations in the low density lipoprotein receptor (LDLR) gene. FH is clinically characterised by an elevated concentration of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), the presence of xanthomata and premature atherosclerosis. The objective of this study was to characterise the LDLR gene mutations in members of a family with FH. In total, 24 individuals were enrolled into this study. A proband from this family was diagnosed as FH based on the Simon Broome's criteria. Mutational screening was performed by polymerase chain reaction - denaturing gradient gel electrophoresis (PCR-DGGE) approach. Those bands that shifted on DGGE were subjected to DNA sequencing to confirm the mutation. We identified a base substitution, T to A at position 763 resulting in substitution of amino acid cysteine (C) to serine (S) at codon 234. This mutation was detected in exon 5 of the LDLR gene which involved the ligand binding domain and is designated as C234S mutation. This domain is important for the binding of LDLR to its ligand, apolipoprotein B100, in order to regulate the LDL catabolism through the LDLR mediated pathway. Mutation in this region may reduce the binding affinity of the LDLR to apolipoprotein B100. To our knowledge, this is a novel mutation worldwide. This mutation could possibly has important clinical implications in view of the high incidence of coronary artery disease (CAD) and sudden cardiac death (SCD) in the family

Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Background and aims: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. Methods: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. Results: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited. Conclusions: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed