AbstractIntroductionFamilial hypercholesterolemia (FH) is most frequently caused by genetic variants in the LDLR gene. Most of LDLR pathogenic variants are missense, followed by splicing and deletion/insertions variants. Mosaicism is a genetic condition in which an individual shows more than one clone of cells with different genotypes.ObjectiveMolecular characterization of a patient with hypercholesterolemia.MethodsGenetic analysis of DNA from peripheral blood and saliva was performed by NGS, sanger sequencing and pyrosequencing technologies.ResultsNGS analysis detected the pathogenic variant LDLR:c.1951G>T:p.(Asp651Tyr) in 9%-12% of reads. The presence of the variant was confirmed by pyrosequencing analysis.ConclusionHerein, we report the first case of a mosaic single nucleotide variant affecting the LDLR gene in a patient with familial hypercholesterolemia. As has been described for other pathologies, mosaicism could be underestimated in FH and its detection will improve with the introduction of NGS technologies in the diagnostic routine.
How registers could enhance knowledge and characterization of genetic dyslipidaemias: The experience of the LIPIGEN in Italy and of other networks for familial hypercholesterolemia
