Affordable Access

Publisher Website

A novel two nucleotide deletion in theapolipoprotein A-Igene,apoA-IShinbashi, associated with high density lipoprotein deficiency, corneal opacities, planar xanthomas, and premature coronary artery disease

Authors
Journal
Atherosclerosis
0021-9150
Publisher
Elsevier
Publication Date
Volume
172
Issue
1
Identifiers
DOI: 10.1016/j.atherosclerosis.2003.09.024
Keywords
  • Apoa-I
  • Hdl Deficiency
  • Coronary Artery Disease
  • Corneal Opacities
  • Xanthomas
Disciplines
  • Biology
  • Design
  • Medicine

Abstract

Abstract Familial HDL deficiency (FHD) is a rare autosomal dominant lipoprotein disorder. We describe a novel genetic variant of the apolipoprotein A-I ( apoA-I) gene resulting in FHD. The proband is a 51-year-old woman who was hospitalized due to severe heart failure. Her plasma HDL-cholesterol (C) and apoA-I concentrations were 0.08 mmol/l and 1 mg/dl, respectively. She exhibited corneal opacities and planar xanthomas on eyelids and elbows. Coronary angiography demonstrated extensive obstructions in two major vessels. Genomic DNA sequencing of the patient’s apoA-I gene revealed a homozygosity for a GC deletion between 5 GC repeats in exon 4, creating a frameshift and a stop codon at residue 178. We designated this mutation as apoA-I Shinbashi. The proband’s father, son, and daughter were found to be heterozygous for this mutation and their HDL-C and apoA-I levels were about half of normal levels, demonstrating a gene dosage effect. The father underwent coronary bypass surgery at age of 70 years. Lecithin–cholesterol acyltransferase (LCAT) activity was decreased by 63% in the homozygote and 31% in heterozygotes, respectively. This new case of apoA-I deficiency, apoA-I Shinbashi, is the first case involving a single gene defect of the apoA-I gene to develop all the characteristics for apoA-I deficiency, including premature coronary heart disease.

There are no comments yet on this publication. Be the first to share your thoughts.