The first hundred families diagnosed with familial hypercholesterolaemia in two lipid clinics in lothian

Abstract

As in other areas of Western Europe, familial hypercholesterolaemia (FH) is one of the most frequent genetic disorders in the UK. Genetic testing for this condition is available in Scotland. This observational study describes the genetic variants found when the databases of the two principal designated lipid clinics in South East Scotland were amalgamated. The genetic mutations were identified by the Molecular Genetics Department in Aberdeen Royal Infirmary by sequencing all 18 exons of the LDLR gene and using multiplex ligation probe amplification (MLPA) to identify major deletions and duplications in the gene. Variants of the APOB gene at codon 3527 and the common PCSK9 mutations were also investigated. The first 100 genetically positive families (as opposed to individuals) were studied and unidentified variants included. Care was taken not to include patients who could be related. Sixty six different genetic mutations were found, including point mutations, major rearrangements, deletions or duplications or unidentified variants. No PCSK9 mutations were found. The frequency of mutations in different exons of the LDLR gene was explored. There was a higher frequency than expected of unclassified variants. Our results were compared with two commercial kits and analysed with the pick-up rate, in this population, disappointing.