In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 15, No. 6 ( 1995-06), p. 773-778
Abstract:
Abstract Cholesterol ester storage disease (CESD) is associated with premature atherosclerosis, hepatomegaly, elevated LDL cholesterol levels, and in most cases, low HDL cholesterol levels. Previous studies have shown a G→A mutation at the 3′ splice junction of exon 8 (E8SJM) of the gene encoding lysosomal acid lipase (LAL) in two kindreds with CESD. In a Canadian-Norwegian kindred with this disease, we show this mutation in conjunction with an as yet unknown T→C transition in exon 10 predicting a Leu 336 →Pro (L336P) replacement and an A→C transversion in exon 2 predicting a T-6P replacement in the prepeptide. Identification of the L336P rather than the T-6P replacement as the second defect underlying CESD in our patient is deduced from three lines of evidence. First, the E8SJM allele is located in cis with the mutation predicting the T-6P–encoding allele but in trans with the L336P-encoding allele; second, the L336P but not the T-6P replacement cosegregates with low LAL activity in the family; third, the T-6P replacement was found in 6 of 28 alleles from subjects with normal lysosomal acid lipase activity, suggesting that this variant represents a frequent nonfunctional polymorphism. Since the residual LAL activity is higher and the clinical phenotype based on plasma lipid values and severity of hepatosplenomegaly is milder in this case than in a previously studied case who was homozygous for the E8SJM allele, we conclude that the L336P variant appears to be associated with a phenotypically mild form of CESD.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/01.ATV.15.6.773
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1995
detail.hit.zdb_id:
1494427-3
