ABCA1 p.Thr940Met
| Predicted by SNAP2: | A: D (80%), C: D (75%), D: D (91%), E: D (91%), F: D (85%), G: D (91%), H: D (91%), I: D (85%), K: D (91%), L: D (91%), M: D (85%), N: D (85%), P: D (91%), Q: D (91%), R: D (91%), S: D (75%), V: D (85%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, V: D, W: D, Y: D, |
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[hide] Update on the molecular biology of dyslipidemias. Clin Chim Acta. 2015 Nov 4. pii: S0009-8981(15)30036-X. doi: 10.1016/j.cca.2015.10.033. Ramasamy I
Update on the molecular biology of dyslipidemias.
Clin Chim Acta. 2015 Nov 4. pii: S0009-8981(15)30036-X. doi: 10.1016/j.cca.2015.10.033., [PMID:26546829]
Abstract [show]
Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. Although secondary factors play a role in clinical expression, dyslipidemias have a strong genetic component. Familial hypercholesterolemia is usually due to loss-of-function mutations in LDLR, the gene coding for low density lipoprotein receptor and genes encoding for proteins that interact with the receptor: APOB, PCSK9 and LDLRAP1. Monogenic hypertriglyceridemia is the result of mutations in genes that regulate the metabolism of triglyceride rich lipoproteins (eg LPL, APOC2, APOA5, LMF1, GPIHBP1). Conversely familial hypobetalipoproteinemia is caused by inactivation of the PCSK9 gene which increases the number of LDL receptors and decreases plasma cholesterol. Mutations in the genes APOB, and ANGPTL3 and ANGPTL4 (that encode angiopoietin-like proteins which inhibit lipoprotein lipase activity) can further cause low levels of apoB containing lipoproteins. Abetalipoproteinemia and chylomicron retention disease are due to mutations in the microsomal transfer protein and Sar1b-GTPase genes, which affect the secretion of apoB containing lipoproteins. Dysbetalipoproteinemia stems from dysfunctional apoE and is characterized by the accumulation of remnants of chylomicrons and very low density lipoproteins. ApoE deficiency can cause a similar phenotype or rarely mutations in apoE can be associated with lipoprotein glomerulopathy. Low HDL can result from mutations in a number of genes regulating HDL production or catabolism; apoAI, lecithin: cholesterol acyltransferase and the ATP-binding cassette transporter ABCA1. Patients with cholesteryl ester transfer protein deficiency have markedly increased HDL cholesterol. Both common and rare genetic variants contribute to susceptibility to dyslipidemias. In contrast to rare familial syndromes, in most patients, dyslipidemias have a complex genetic etiology consisting of multiple genetic variants as established by genome wide association studies. Secondary factors, obesity, metabolic syndrome, diabetes, renal disease, estrogen and antipsychotics can increase the likelihood of clinical presentation of an individual with predisposed genetic susceptibility to hyperlipoproteinemia. The genetic profiles studied are far from complete and there is room for further characterization of genes influencing lipid levels. Genetic assessment can help identify patients at risk for developing dyslipidemias and for treatment decisions based on 'risk allele' profiles. This review will present the current information on the genetics and pathophysiology of disorders that cause dyslipidemias.
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No. Sentence Comment
1061 One patient was identified to be homozygous for a nonsense mutation p. Q1038X, a further kindred showed compound heterozygosity for missense variants p. R937V and p.T940M, and a third pedigree was compound heterozygous for a frameshift variant p.I1200Hfs*4 and an intronic variant that lead to the creation of a cryptic splice site and premature truncation p. S1392Rfs*6.
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ABCA1 p.Thr940Met 26546829:1061:165
status: NEW