Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Generalised lipodystrophy of the Berardinelli-Seip type (BSCL) is a rare autosomal recessive human disorder with severe adverse metabolic consequences. A gene on chromosome 9 (BSCL1) has recently been identified, predominantly in African-American families. More recently, mutations in a previously undescribed gene of unknown function (BSCL2) on chromosome 11, termed seipin, have been found to be responsible for this disorder in a number of European and Middle Eastern families. We have studied the genotype/phenotype relationships in 70 affected subjects from 44 apparently unrelated pedigrees of diverse ethnic origin. In all subjects, hepatic dysfunction, hyperlipidaemia, diabetes mellitus, and hypertrophic cardiomyopathy were significant contributors to morbidity with no clear differences in their prevalence between subjects with BSCL1 or BSCL2 and those with evidence against cosegregation with either chromosome 9 or 11 (designated BSCLX). BSCL2 appears to be a more severe disorder than BSCL1 with a higher incidence of premature death and a lower prevalence of partial and/or delayed onset of lipodystrophy. Notably, subjects with BSCL2 had a significantly higher prevalence of intellectual impairment than those with BSCL1 or BSCLX (p<0.0001, OR 17.0, CI 3.6 to 79.0). The higher prevalence of intellectual impairment and the increased risk of premature death in BSCL2 compared to BSCL1 emphasise the importance of molecular diagnosis of this syndrome and have clear implications for genetic counselling.
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PMID:Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy. 1236 29

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by marked lack of body fat since birth, which results in striking muscular appearance. Patients develop extreme insulin resistance and its complications, such as diabetes, hyperlipidemia and fatty liver. Mutations in the BSCL2 (which encodes seipin, a protein of unknown function) and AGPAT2 (which encodes 1-acylglycerol-3-phosphate O-acyltransferase 2) genes have been reported in patients with CGL. AGPAT2 is a key enzyme involved in triglyceride and phospholipid biosynthesis and, thus, the discovery of AGPAT2 mutations has heightened interest in the biochemical pathways of triglyceride synthesis and their implications in human physiology and in the pathophysiology of obesity, lipodystrophies and other adipose tissue disorders. All enzymes involved in triglyceride synthesis, including AGPAT, have several known isoforms encoded by different genes. Assuming different substrate specificities of these enzymes, the human body might have many forms of triglycerides and phospholipids. Here, we discuss the significance of these in energy storage, in addition to the normal functioning of cell membranes.
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PMID:Congenital generalized lipodystrophy: significance of triglyceride biosynthetic pathways. 1282 27