Familial apolipoprotein A-I, C-III, and A-IV deficiency and premature atherosclerosis due to deletion of a gene complex on chromosome 11
Population
A kindred with marked plasma high density lipoprotein deficiency and premature atherosclerosis, including 1…
Design
Case_series
Authors
Discussion
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Member takes
Implication
Supports HDL's independent role in atherosclerosis; hypothesis-generating from single case report, needs validation.
Key Points
- Investigate the molecular genetic defect causing severe high-density lipoprotein deficiency and premature coronary artery atherosclerosis in an affected kindred.
- Evaluated a homozygous proband with fatal premature atherosclerosis and examined lipid and apolipoprotein profiles across 10 heterozygous family members.
- Conducted restriction fragment length polymorphism analysis using multiple restriction enzymes (BamHI, EcoRI, HindIII, XmnI, PstI, and PvuII) and a 1.1-kb genomic probe 2.5 kb upstream of the apoA-I gene.
- Performed genomic cloning and DNA sequence analysis across the mutated chromosome 11 allele.
- The homozygous proband demonstrated undetectable plasma apoA-I and apoC-III, while 10 heterozygotes exhibited mean apoA-I, apoC-III, apoA-IV, and HDL cholesterol levels at 67%, 57%, 65%, and 62% of normal values, respectively.
- Sequence analysis confirmed the complete deletion of the apoA-I, apoC-III, and apoA-IV gene complex on chromosome 11, with both deletion endpoints mapped within repetitive DNA regions.
Structured PICO
P
Population
A kindred with marked plasma high density lipoprotein (HDL) deficiency and premature atherosclerosis, including 1 homozygous proband and 10 heterozygotes.
C
Comparator
Normal subjects (implied by comparison of apolipoprotein and HDL levels)
O
Outcome
Identification of the genetic defect causing familial apolipoprotein A-I, C-III, and A-IV deficiencysurrogate
The complete deletion of the apoA-I, -C-III, and -A-IV gene complex on chromosome 11 causes marked HDL deficiency and premature atherosclerosis, supporting an independent role for HDL in the pathogenesis of atherosclerosis.
Cite This Study
Ordovás et al. (1989) studied this question.