compound homozygous mutations in ldlr and pcsk9 genes cause premature cad in a family

Background and aim: homozygous familial hypercholesterolemia is a rare inherited metabolic disease caused by low-density lipoprotein receptor abnormality increasing the chance of cvd development that usually occurs in the first decade of life. mutations in ldlr account for 60%-80% of patients with fh. mutations in pcsk9 gene are less common than mutation in ldlr and account for 3% of patients with fh. here, we report a 11-year-old girl with an unpredicted presentation for coronary artery disease and found to have homozygous familial hypercholesterolemiamethods: a 11-year-old girl from south (kerman) of iran was admitted to cardiogenetic research center of rajaie cardiovascular, medical, and research center with premature cad and positive family history of hypercholesterolemia. she was born to consanguineous parents and has 2 little brothers that all have high level of cholesterol. the pedigree of 3 generations for this family was draw. the dna was extracted from the whole blood of the proband, her siblings and parents. the whole coding exons, exon-intron junctions, and important regions of introns in the ldlr and pcsk9 genes were amplified and sequenced.results: our results revealed compound homozygous mutations in ldlr and pcsk9 genes in a girl of the family and heterozygous mutations for both ldlr and pcsk9 genes in parents. the older brother has a heterozygous mutation in ldlr and homozygous mutation in pcsk9 gene. the younger one has only heterozygous mutation in ldlr gene. conclusion: although the mutation of pcsk9 is a loss of function one, a 11-year-old girl of the family presents a severe premature cad due to the homozygous mutation in ldlr gene. children with homozygous familial hypercholesterolemia may present with symptoms of premature cad disease needing a routine lipid test and careful anamnesis.