Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 60-year-old white male (KH) was diagnosed to suffer from severe type III hyperlipoproteinemia (HLP) and premature cardiovascular disease. Biochemical analysis revealed an unusual apolipoprotein (apo) E phenotype and genotype. All clinical characteristics of type III HLP were present in the patient. His very low density lipoprotein (VLDL) cholesterol to plasma triglyceride (TG) ratio was elevated at 0.97 without therapy which is unusually high (normal ratio about 0.18). By contrast his plasma apo E level was only moderately elevated (6.8 mg dl-1). The patient's apo E migrated in the apo E1 position on isoelectric focusing gels. Chemical modification with cysteamine and treatment with neuraminidase confirmed the presence of two cysteine residues in the patient's apo E and a normal sialylation pattern. Pedigree analysis suggested that the patient was a compound heterozygote with one apo epsilon 1 allele and another allele whose product did not appear in the plasma compartment ('null' allele). Direct sequencing of polymerase chain reaction (PCR) amplified segments of the apo E gene as well as restriction fragment length polymorphism (RFLP) analysis with the endonuclease Taq I identified an adenosine for guanosine (G-->A) exchange in the second base of codon 127 that is predictive for an Asp for Gly substitution in the encoded apo E amino acid sequence. This mutation is the structural basis for the apo E1 isoform identified upon isoelectric focusing. Five other family members are also carriers of the mutant apo epsilon 1 allele. Two of those were hyperlipidemic and exhibited biochemical characteristics of type III HLP. A second mutation, a deletion of a G in codon 31, is predictive for a reading frameshift that encodes for a premature stop in codon 60. Our inability to identify the product of a second apo E allele in the plasma of the patient and two other members of the KH family corresponds with the heterozygous presence of this mutation in the affected individuals. Both relatives (like the index case) had an increased VLDL cholesterol to plasma TG ratio, which indicates the presence of cholesterol-enriched VLDL particles. We propose that the single base deletion in the apo E gene which is the cause of a non-functional 'null' allele in addition to a probably dominant apo E1 (Gly127-->Asp, Arg158-->Cys) variant of late or incomplete penetrance are the primary genetic defects in this kindred leading to severe dysbetalipoproteinemia.
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PMID:Severe type III hyperlipoproteinemia associated with unusual apolipoprotein E1 phenotype and epsilon 1/'null' genotype. 136 Aug 98

In the process of screening apolipoprotein (apo) E genotypes in a population of subjects with lipid abnormalities, we have identified five subjects (one homozygote and four heterozygotes) with an abnormal 109 base pairs band following apo E restriction isotyping of amplified DNA with the restriction endonuclease CfoI. The polymerase chain reaction (PCR) products were cloned and their sequencing revealed a C-->A substitution at the first nucleotide of codon 136. This mutation resulted in an amino acid substitution Arg to Ser, previously described as apo E2 Christchurch. Family studies were carried out for four of the probands. In these kindreds, stepwise multiple regression analyses indicated that 78% of the cholesterol variability in men was predicted by body mass index, age and the rare apo E2 (Arg136-->Ser) variant. In women, age and the apo E2 (Arg136-->Ser variant predicted 54.9% of the variability in cholesterol levels. Linkage analysis suggested that the presence of the apo E2 (Arg136-->Ser) variant was linked with the occurrence of cholesterol enriched triglyceride rich lipoproteins and with an incomplete dominance of type III hyperlipoproteinemia. Our data indicates that this mutation may be a relatively common cause of dyslipidemia in the Spanish population.
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PMID:Incomplete dominance of type III hyperlipoproteinemia is associated with the rare apolipoprotein E2 (Arg136-->Ser) variant in multigenerational pedigree studies. 872 10

Apolipoprotein (apo) E mediates the removal of chylomicron and very low density lipoprotein remnants from plasma. It is polymorphic in sequence and the products of the three common alleles (epsilon 2, epsilon 3, epsilon 4) differ from one another in their binding to lipoprotein receptors. ApoE2 is defective in binding and homozygosity for apoE2 is associated with type III hyperlipoproteinemia (HLP). Other rare isoforms of apoE have been found to be associated either with dominant type III HLP or with the development of hypertriglyceridemia. We identified a 42 year-old hypertriglyceridemic woman with an apoE phenotype 3/1. Restriction isotyping using AflIII/HaeII resulted in an apparent apoE genotype 3/2, suggesting that the mutation occurred in an epsilon 2 allele. DNA sequence analysis revealed a C-->T point mutation at the first position of the codon for amino acid residue 180 of the mature apoE. This predicted a change Arg(180)-->Cys. The mutation altered a recognition site for the endonuclease HaeII, which allowed us rapidly to screen for this mutation. In relatives of the proband, apoE1 Baden was consistently associated with hypertriglyceridemia. Similar to other apoE variants linked to hypertriglyceridemia, the Arg(180)-->Cys mutation is located within the lipid binding domain of apoE. We therefore suggest that apoE1 Baden may cause hypertrigylceridemia, possibly by inhibiting the hydrolysis of triglycerides associated with very low density lipoproteins.
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PMID:Apolipoprotein E1 Baden (Arg(180)-->Cys). A new apolipoprotein E variant associated with hypertriglyceridemia. 1116 21