Homozygous familial hypercholesterolemia: The c.1055G>A mutation in the LDLR gene and clinical heterogeneity

Abstract Familial hypercholesterolemia (FH) is a world public health issue because of its high frequency, morbidity, and mortality. FH is characterized by elevated plasma low-density lipoprotein cholesterol (LDL-C) levels and a high risk for premature cardiovascular disease. We report an 8-year-old male with homozygous familial hypercholesterolemia. The clinical and biochemical characteristics of this case were bilateral corneal arcus, xanthomas in several body parts, severe stenosis of the left carotid artery and serum total cholesterol levels of 782.0 mg/dL and 715.0 mg/dL LDL-C. The initial treatment was atorvastatin (40 mg) and ezetimibe (20 mg), with no satisfactory response. LDLR gene was analyzed and homozygosity for c.1055G>A mutation was observed, resulting in an amino acid change from cysteine to tyrosine in codon 352 (p.Cys352Tyr). This mutation is known as Mexico 2 and has only been observed in the Mexican population. Both parents and siblings were carriers of the same mutation, but the paternal grandmother and the father of the index case showed the phenomenon of incomplete penetrance. With the analysis 5 polymorphisms (rs1003723C>T, rs5930A>G, rs688C>T, rs5929T>C and rs5927A>G), a common ancestor for the mutation can be suggested and linkage to TGTCG haplotype.