Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial hypobetalipoproteinemia is an autosomal co-dominant disorder, which in a minority of cases is due to a truncation producing mutation in the apoB gene. We have identified an apoB mutation in a 40-year old hypobetalipoproteinemic man with Type II diabetes mellitus. Immunoblotting of plasma revealed a major band for apoB-100 and a minor band with estimated size between apoB-52 and apoB-55. The proband's 75-year old father with Type II diabetes and a non-diabetic daughter also possessed the truncated protein. Direct sequencing of the amplified fragment of genomic DNA revealed a C-->T transition at nt 7692 in exon 26 of the apoB gene. This substitution yielded a premature stop codon at residue 2495 and abolished a BsaI restriction endonuclease site. The identical mutation has been described previously; however, the genotypes and ancestors of the kindred were different, suggesting that the mutation may have occurred independently. The majority of apoB-55 was eluted as particles smaller than LDL-sized apoB-100, and floated mostly between the LDL and HDL density range. It is worth noting that despite the presence of Type II diabetes, both the proband and his father have very low plasma lipid levels and neither have any clinically manifest macrovascular complications.
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PMID:Diabetes mellitus in a new kindred with familial hypobetalipoproteinemia and an apolipoprotein B truncation (apoB-55). 954

Familial hypobetalipoproteinemia is caused by mutations in the apolipoprotein (apo) B gene. We identified a 57-year-old woman whose plasma total cholesterol and apoB levels were 2.17 mmol/L and 0.03 g/L, respectively. Separation of plasma lipoproteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the absence of apoB-100 and the presence of a faster-migrating form of apoB with an apparent Mr of 195 kDa. Direct sequencing of a polymerase chain reaction-amplified fragment of the patient's apoB gene DNA revealed a single C-->T transition at nucleotide 5472 that converts glutamine 1755 (CAA) to a stop codon (TAA). We predict this novel nonsense mutation of the apoB gene to produce a truncated protein that contains 1754 amino-terminal amino acid residues of apoB-100. We designated this mutant form of apoB apoB-38.7 by following the centile nomenclature of the apoB species. The same mutation was found in both of her children. The proband revealed clinical findings of retinitis pigmentosa, acanthocytosis, and loss of deep tendon reflexes that are characteristic of severe hypobetalipoproteinemia. In addition, the proband had type II diabetes mellitus with nephropathy, anemia, cholelithiasis, hepatic hemangioma, bronchiectasis, and extensive calcification of major arteries including, the celiac, splenic, and renal. In summary, we have found a novel truncated apoB, apoB-38.7, in a patient with an unusual presentation of hypobetalipoproteinemia that includes diabetes mellitus and extensive arterial calcification.
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PMID:A truncated species of apolipoprotein B (B-38.7) in a patient with homozygous hypobetalipoproteinemia associated with diabetes mellitus. 971 41

Fatty liver disease is now recognized as a major health burden, due to the greater number of cases that are being diagnosed. This trend could partly be explained by the increased use of liver ultrasonography in asymptomatic patients for various reasons, mainly persistent transaminase elevation. The most commonly reported risk factors associated with fatty liver disease are chronic alcohol intake, obesity, type 2 diabetes mellitus, hyperlipidemia, and some drugs. When these factors have been ruled out in a patient with a fatty liver, less frequent causes such as certain inherited metabolic disorders should be considered. Familial hypobetalipoproteinemia is characterized by an alteration of apolipoprotein B (apo B) synthesis, leading to the secretion of truncated forms of the protein, which in turn leads to a marked reduction in excretion of very low-density lipoproteins from the liver and consequently to lipid deposits, especially triglycerides, in the hepatocytes. We report the case of a 23-year-old man who met the diagnostic criteria for heterozygous familial hypobetalipoproteinemia. He presented with mild transaminase elevation and fatty liver. Total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and apo B were below normal limits, while levels of high-density lipoprotein cholesterol were normal. Lipid profile determination and liver ultrasonography of first and second-degree relatives were also performed. Molecular studies of the index case revealed an unaffected apo B gene.
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PMID:[Hepatic steatosis associated with heterozygotic familial hypobetalipoproteinemia]. 1505 12