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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
1995-7-10
|
| pubmed:abstractText |
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 Leu336-->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.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, HDL,
http://linkedlifedata.com/resource/pubmed/chemical/Lipase,
http://linkedlifedata.com/resource/pubmed/chemical/Triglycerides,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Galactosidase
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
1079-5642
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
15
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
773-8
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:7773732-Adult,
pubmed-meshheading:7773732-Alleles,
pubmed-meshheading:7773732-Amino Acid Sequence,
pubmed-meshheading:7773732-Base Sequence,
pubmed-meshheading:7773732-Cholesterol,
pubmed-meshheading:7773732-Cholesterol, HDL,
pubmed-meshheading:7773732-Cholesterol Ester Storage Disease,
pubmed-meshheading:7773732-Exons,
pubmed-meshheading:7773732-Female,
pubmed-meshheading:7773732-Heterozygote,
pubmed-meshheading:7773732-Humans,
pubmed-meshheading:7773732-Lipase,
pubmed-meshheading:7773732-Lymphocytes,
pubmed-meshheading:7773732-Lysosomes,
pubmed-meshheading:7773732-Male,
pubmed-meshheading:7773732-Molecular Sequence Data,
pubmed-meshheading:7773732-Mutation,
pubmed-meshheading:7773732-Phenotype,
pubmed-meshheading:7773732-Sequence Analysis, DNA,
pubmed-meshheading:7773732-Triglycerides,
pubmed-meshheading:7773732-beta-Galactosidase
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
A novel variant of lysosomal acid lipase (Leu336-->Pro) associated with acid lipase deficiency and cholesterol ester storage disease.
|
| pubmed:affiliation |
Institut für Arterioskleroseforschung, Westfälische Wilhelms-Universität, Germany.
|
| pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, Non-U.S. Gov't
|