Familial Hypercholesterolemia Research Paper

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Familial Hypercholesterolemia Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the genes coding for the low density lipoprotein receptor (LDLR) (Waqas et all., 2013). The aim of this work is to present a description of the disorder as well as inheritance patterns. Familial Hypercholesterolemia is a genetic disorder that includes various inheritance patterns*. Description of Familial Hypercholesterolemia Familial hypercholesterolemia, also spelled familial hypercholestrolaemia, is a genetic autosomal dominant disorder that has been caused by multiple mutations in low-density lipoprotein (LDL) receptor gene (Nemati & Astaneh, 2013). Without any functioning low-density lipoprotein receptors (LDLR) catabolism…show more content…
*“In certain populations, a small number of mutations predominate due to founder effects and therefore, there is a high heFH frequency in these populations including French Canadians,11 Christian Lebanese,12 Druze,13 Finns,14 South African Afrikaner,15 and Ashkenazi Jews of Lithuanian descent” (Castro-Oros, Pocovi, & Civeira, 2010). First Described Case and Founder Originally, FH was first described by Dr. Carl Müller in 1938. The FH defect was initially thought to be the result of cholesterol over synthesis. However, in the mid-1970s, Michael S. Brown and Joseph L. Goldstein found that the FH defect was actually due to the absence of high affinity receptor for the uptake of serum LDL (Castro-Oros, Pocovi, & Civeira, 2010). These men had defined the LDLR pathway with its implications in other pathways and identified the certain genetic defect that caused impairment in the LDLR (Castro-Oros, Pocovi, & Civeira, 2010). Astonishingly, one of the first reports of FH presented an important association between coronary heart disease and clinical FH. This was the study done by Slack near the beginning of the second half of the 20th century (Huijen et all.,…show more content…
A third putative locus for FH is located on a region on chromosome 1 encoding the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein” (Huijen et all., 2008). There has been found to be variations in the PCSK9 and they are found to be a rare cause of non-LDLR/non-ApoB FH. Up to date, there has been eight hypercholesterolemic missense mutations in PCSK9 have been found (Huijen et all., 2008). These mutations in the PCSK9 gene have been associated with both hypercholesterolemia and hypocholesterolemia from mechanisms that involve a loss-of-function and a gain-of-function (Huijgen et all., 2008). “A prominent hypothesis states that gain-of-function mutations in PCSK9 cause hypercholesterolemia due to a process in which PCSK9 stimulates the redistribution from LDL-R proteins from the cell membrane to lysosomes in hepatocytes and through this mechanism enhances degradation of LDL-R” (Huijgen et all., 2008). Mutations that have been found to result in a loss of function have decreased LDL-C levels. However, neither in the definite role of PCSK9 in cholesterol metabolism, nor in the influence of any genetic variation in this PCSK9 gene is exemplified* (Huijgen et all.,

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