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| APOLIPOPROTEIN-A-I Q[-2]X CAUSING ISOLATED APOLIPOPROTEIN-A-I DEFICIENCY IN A FAMILY WITH ANALPHALIPOPROTEINEMIA |
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| Author(s): NG DS, LEITER LA, VEZINA C, CONNELLY PW, HEGELE RA |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 93 Issue: 1 Pages: 223-229 Published: JAN 1994 |
| Times Cited: 67 References: 52 |
| Abstract: We report a Canadian kindred with a novel mutation in the apolipoprotein (apo)A-I gene causing analphalipoproteinemia. The 34-yr-old proband, product of a consanguineous marriage, had bilateral retinopathy, bilateral cataracts, spinocerebellar ataxia, and tendon xanthomata. High density lipoprotein cholesterol (HDL-C) was < 0.1 mM and apoA-I was undetectable. Genomic DNA sequencing of the proband's apoA-I gene identified a nonsense mutation at codon [-2], which we designate as Q [-2] X. This mutation causes a loss of endonuclease digestion sites for both BbvI and Fnu4HI. Genotyping identified four additional homozygotes, four heterozygotes, and two unaffected subjects among the first-degree relatives. Q [-2]X homezygosity causes a selective failure to produce any portion of mature apoA-I, resulting in very low plasma level of HDL. Heterozygosity results in approximately half-normal apoA-I and HDL. Gradient gel electrophoresis and differential electroimmunodiffusion assay revealed that the HDL particles of the homozygotes had peak Stokes diameter of 7.9 nm and contained apoA-II without apoA-I (Lp-AII). Heterozygotes had an additional fraction of HDL(3)-like particles. Two of the proband's affected sisters had documented premature coronary heart disease. This kindred, the third reported apoA-I gene mutation causing isolated complete apoA-I deficiency, appears to be at significantly increased risk for atherosclerosis. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV TORONTO, ST MICHAELS HOSP, DEPT MED, DNA RES LAB, TORONTO, ON M5B 1A6 CANADA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: MY159 |
| ISSN: 0021-9738 |
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