The first ninety families diagnosed with mutation positive familial hypercholesterolaemia in two lipid clinics in a Scottish Health Board area

R. M. Finnie, S. Walker, W. G. Simpson, Z. Miedzybrodzka

Research output: Contribution to journalAbstractpeer-review


The publication of the NICE Guideline on Identification and Management of Familial Hypercholesterolaemia (FH) in 2008, served as a catalyst for the Scottish Lipid Forum to implement a system of genetic and cascade screening for familial heterozygous hypercholesterolaemia (FH) in Scotland. We describe the first ninety mutation positive families identified in one Health Board area where the prevalence is estimated at 1000 cases. There are two designated Lipid Clinics and also a two further clinics that deal with Lipid problems. These two designated Lipid clinics amalgamated their databases in 2010 and the mutations of these first ninety families identified as genetically positive for familial hypercholesterolaemia are described. The positive pickup rate from all samples sent was 34% similar to other studies. When there was a possible family connection between two probands only one was included. Unclassified variants were also included. Sixty-five families were identified at one centre and twenty-five at the other. The male:female ratio of probands was not significantly different. There were no reports of the PCSK9 (Arg374Tyr) mutation, ten unclassified variants were found and seven Apo B 3500 (c.1058G>A; p.Arg3527Gln) mutations. LDLR MPLA showed evidence of four duplications of exons 11–12, three deletions of exon 1, a single deletion involving 2–6, a single deletion involving exons 3–6 and also a single deletion of exons 11–12.LDL sequencing yielded seven c.660delC; p.Asp221Trhfx44 mutations, five c.1444G>A; p.Asp482Asn, five c.682G>T; p.Glu228X, four c.2054C>T; p.Pro685Leu, three c.933delA; p.Glu312SerfsX58, and two c.313+1G>A mutations with a further 37 different point mutations being identified. Of particular note is that commercially available kits would only have picked up 34% (FH20) or 57% (FH48) of these mutations. Conclusion: Gene sequencing is necessary for all possible new cases of FH in small geographical areas.
Original languageEnglish
Pages (from-to)e3
Number of pages1
Issue number2
Publication statusPublished - Oct 2011
Event25th Annual Conference on Heart - Warwick, United Kingdom
Duration: 6 Jul 20118 Jul 2011

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