lunes, 9 de junio de 2014

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

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



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

Received 20 March 2014; received in revised form 12 May 2014; accepted 18 May 2014. published online 26 May 2014.
Accepted Manuscript

Abstract 

Familial hypercholesterolemia (FH) is a world public health issue, due to its high frequency and its morbidity and mortality. FH is characterized by elevated plasma low-density lipoprotein cholesterol (LDL-C) levels and high risk for premature cardiovascular disease. We report a patient of 8 year-old male with homozygous familial hypercholesterolemia. The clinical and biochemical characteristics of the index 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 (40mg) and ezetimibe (20mg), 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 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 five 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.

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