Severe HDL deficiency due to novel defects in the ABCA1 transporter

Novel mutations of ABCA1 transporter in patients with Tangier disease and familial HDL deficiency

“…Genomic DNA was extracted from peripheral blood leukocytes by a standard procedure; the promoter and the 50 exons and the exonintron junctions of the ABCA1 gene were amplified and sequenced as reported previously [13]. The analysis of the APOA-I and LCAT genes was performed as reported [14,15].…”

The curious case of the orange coloured tonsils

“…Absence of the ABCA1 transporter leads to a defect in cellular cholesterol removal, resulting in severe deficiency of plasma levels of HDL-C and ApoA-1, reduced LDL-C and normal or elevated triglycerides [9][10][11]. The clinical presentation of Tangier disease is related to the accumulation of cholesterol in the macrophages of peripheral tissues, which include tonsils, spleen, liver, lymph nodes, thymus, intestinal mucosa, peripheral nerves and cornea [12].…”

A Non-classical Presentation of Tangier Disease with Three ABCA1 Mutations

“…The W1699C and Y1532C mutations have been described in the literature as having some residual function (Pisciotta et al 2009;Cameron et al 2010), where as A1046D mutations causes severe loss of gene product and its function. Because of her phenotype and a heterozygous genotype, the chromosome with only one mutation may have a milder mutation that still provides some function to the transporter, thus giving her a non-classic phenotype.…”

“…All three of these mutations have been reported to be deleterious in functional studies. The p.A1046D mutation has been found to abolish cholesterol efflux (Pisciotta et al 2009). The p.Y1532C (Cameron et al 2010) and p.W1699C (Pisciotta et al 2009) have been found to prevent the mutant proteins from exiting the endoplasmic reticulum.…”