Multiple splice defects in ABCA1cause low HDL-C in a family with Hypoalphalipoproteinemia and premature coronary disease

Abstract

Background: Mutations at splice junctions causing exon skipping are uncommon compared to exonic mutations, and two intronic mutations causing an aberrant phenotype have rarely been reported. Despite the high number of functional ABCA1 mutations reported to date, splice variants have been reported infrequently. We screened DNA from a 41 year-old male with low HDL-C (12 mg/dL [0.31 mmol/L]) and a family history of premature coronary heart disease (CHD) using polymerase chain reaction single-strand conformation polymorphism (SSCP) analysis.

A case report of a diabetic woman with very low HDL cholesterol

“…13 Therefore single-gene abnormalities responsible for HDLc deficiency states may have variable effects on cardiac risk. [10][11][12][13] The most common conditions that cause hypertriglyceridemia are associated with premature CAD, including familial combined hyperlipidemia and familial hypoalphalipoproteinemia, each affecting approximately 1% of the population. 13 Many patients with type 2 diabetes develop a lipoprotein phenotype marked by elevated TGs and low HDLc.…”

“…Reduced levels of a-1, a-2 lipoproteins (LPs) and elevated levels of the a-3 LPs as detected in this case are known to be associated with CAD. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] This pattern is usually not seen in isolated forms of familial hypertriglyceridemia and is most frequently observed in subtypes of heterozygous Tangier disease. 2 The family history of premature CAD, decreased levels of a-1 and a-2 LPs (big HDL) along with increased a-3 LP (small HDL) warrant medication and life style modification.…”

“…[10][11][12][13] The most common conditions that cause hypertriglyceridemia are associated with premature CAD, including familial combined hyperlipidemia and familial hypoalphalipoproteinemia, each affecting approximately 1% of the population. 13 Many patients with type 2 diabetes develop a lipoprotein phenotype marked by elevated TGs and low HDLc. 14 Together, these three disorders have been reported to account for up to 50% of premature CAD events.…”

“…2 The family history of premature CAD, decreased levels of a-1 and a-2 LPs (big HDL) along with increased a-3 LP (small HDL) warrant medication and life style modification. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] The normal apoA-I concentrations would essentially rule out any known variant of cholesterol transporters such as Tangier disease, LCAT deficiency, or variants of the apoA-I gene. The possibility of hypertriglyceridemia with some coincidental gain of function in the cholesteryl ester transfer protein might be considered, but we have no evidence to support that.…”

“…Measurement of LP levels after treatment demonstrated desirable increases in the a-1 and a-2 LPs and diminished a-3 LPs, which may be associated with decreased CAD risk [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. …”