Palacios L et al. – This study analyzes the mutation spectrum in Spain, remarks the importance of genetic diagnosis of familial hypercholesterolemia (FH) patients, as well as the cascade screening, and shows how it is being carried out in Spain.Methods
- The authors have analyzed 5430 Spanish index cases and 2223 relatives since 2004 with LIPOchip genetic diagnostic platform, a microarray for the detection of Spanish common mutations in these three genes, including copy number variation (CNV) in LDLR, followed by sequencing analysis of the coding regions of LDLR and exon 26 of APOB, when the result is negative.
- Samples were received from hospitals of all around Spain.
- The preferred clinical criterion to diagnose FH was Dutch Lipid Clinic Network (DLCN) score.
- The results show that there is a broad spectrum of mutations in the LDLR gene in Spain since about 400 different mutations were detected, distributed along almost the whole LDLR gene.
- Mutations in APOB (mainly p.Arg3527Gln) covered 6.5% of positive cases and only one PCSK9 mutation was detected.
- The authors found correlation between more severe mutations and the clinical diagnosis but also that 28% of FH patients harboring mutations do not have a definite clinical diagnosis.