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Center for Nephrology and Metabolic Disorders
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Combined familial hyperlipidemia with dysfunctional LDL clearance

Combined familial hyperlipidemia with dysfunctional LDL clearance is a group of disorder in which mutations cause an impaired eleimination of LDL from plasma.

Systematic

Familial combined Hyperlipemia
Combined familial hyperlipidemia with VLDL overproduction
Combined familial hyperlipidemia with adipose tissue dysfunction
Combined familial hyperlipidemia with dysfunctional LDL clearance
ATF6
LDLR
PCSK9
Combined familial hyperlipidemia with dysfunctional VLDL metabolism

References:

1.

Takada D et al. (2002) Interaction between the LDL-receptor gene bearing a novel mutation and a variant in the apolipoprotein A-II promoter: molecular study in a 1135-member familial hypercholesterolemia kindred.

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2.

Teslovich TM et al. (2010) Biological, clinical and population relevance of 95 loci for blood lipids.

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3.

Lewis MJ et al. (2009) Immunoglobulin M is required for protection against atherosclerosis in low-density lipoprotein receptor-deficient mice.

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4.

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5.

Lindgren V et al. (1985) Human genes involved in cholesterol metabolism: chromosomal mapping of the loci for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A reductase with cDNA probes.

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6.

Aulchenko YS et al. (2009) Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.

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7.

Takada D et al. (2003) Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol phenotype in familial hypercholesterolemia: intra-familial association study in an eight-generation hyperlipidemic kindred.

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8.

Lin JH et al. (2007) IRE1 signaling affects cell fate during the unfolded protein response.

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9.

Hai TW et al. (1989) Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers.

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10.

Zhu C et al. (1997) Interaction of ATF6 and serum response factor.

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11.

Yoshida H et al. (1998) Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. Involvement of basic leucine zipper transcription factors.

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12.

Haze K et al. (1999) Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress.

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13.

Li M et al. (2000) ATF6 as a transcription activator of the endoplasmic reticulum stress element: thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1.

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14.

Ye J et al. (2000) ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs.

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15.

Sommer T et al. (2002) BiP binding keeps ATF6 at bay.

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16.

Shen J et al. (2002) ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals.

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17.

Thameem F et al. (2006) Association of amino acid variants in the activating transcription factor 6 gene (ATF6) on 1q21-q23 with type 2 diabetes in Pima Indians.

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18.

Meex SJ et al. (2007) Activating transcription factor 6 polymorphisms and haplotypes are associated with impaired glucose homeostasis and type 2 diabetes in Dutch Caucasians.

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19.

Higa A et al. (2014) Endoplasmic reticulum stress-activated transcription factor ATF6α requires the disulfide isomerase PDIA5 to modulate chemoresistance.

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20.

Kohl S et al. (2015) Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia.

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21.

Ansar M et al. (2015) Mutation of ATF6 causes autosomal recessive achromatopsia.

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22.

Varret M et al. (1997) Software and database for the analysis of mutations in the human LDL receptor gene.

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23.

Cohen JC et al. (2006) Sequence variations in PCSK9, low LDL, and protection against coronary heart disease.

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24.

Lambert G et al. (2006) Fasting induces hyperlipidemia in mice overexpressing proprotein convertase subtilisin kexin type 9: lack of modulation of very-low-density lipoprotein hepatic output by the low-density lipoprotein receptor.

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25.

Zhao Z et al. (2006) Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote.

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26.

Benjannet S et al. (2006) The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications.

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27.

Mayne J et al. (2007) Plasma PCSK9 levels correlate with cholesterol in men but not in women.

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28.

Kwon HJ et al. (2008) Molecular basis for LDL receptor recognition by PCSK9.

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29.

Schmidt RJ et al. (2008) Secreted proprotein convertase subtilisin/kexin type 9 reduces both hepatic and extrahepatic low-density lipoprotein receptors in vivo.

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30.

Kathiresan S et al. (2008) A PCSK9 missense variant associated with a reduced risk of early-onset myocardial infarction.

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31.

Kotze MJ et al. (1991) The molecular basis and diagnosis of familial hypercholesterolaemia in South African Afrikaners.

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32.

Oppenheim A et al. (1991) Hypercholesterolemia in five Israeli Christian-Arab kindreds is caused by the "Lebanese" allele at the low density lipoprotein receptor gene locus and by an additional independent major factor.

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33.

Benlian P et al. (1990) A LDL receptor gene homozygous mutation: PCR amplification, direct genomic sequencing, associated haplotype, rapid screening for frequency.

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34.

Top B et al. (1990) Rearrangements in the LDL receptor gene in Dutch familial hypercholesterolemic patients and the presence of a common 4 kb deletion.

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35.

Lelli N et al. (1991) Duplication of exons 13, 14 and 15 of the LDL-receptor gene in a patient with heterozygous familial hypercholesterolemia.

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36.

Hobbs HH et al. (1990) The LDL receptor locus in familial hypercholesterolemia: mutational analysis of a membrane protein.

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37.

Leitersdorf E et al. (1990) Common low-density lipoprotein receptor mutations in the French Canadian population.

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38.

Kotze MJ et al. (1990) An exon 4 mutation identified in the majority of South African familial hypercholesterolaemics.

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39.

Ruffner DE et al. (1987) Invasion of the human albumin-alpha-fetoprotein gene family by Alu, Kpn, and two novel repetitive DNA elements.

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40.

Yamakawa K et al. (1989) Three novel partial deletions of the low-density lipoprotein (LDL) receptor gene in familial hypercholesterolemia.

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41.

Boehnke M et al. (1989) Fine-structure genetic mapping of human chromosomes using the polymerase chain reaction on single sperm: experimental design considerations.

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42.

Leitersdorf E et al. (1989) Two common low density lipoprotein receptor gene mutations cause familial hypercholesterolemia in Afrikaners.

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43.

Taylor R et al. (1989) A study of familial hypercholesterolaemia in Iceland using RFLPs.

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44.

Frank SL et al. (1989) Linkage of the mouse LDL receptor gene on chromosome 9.

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45.

Soutar AK et al. (1989) Identification of a point mutation in growth factor repeat C of the low density lipoprotein-receptor gene in a patient with homozygous familial hypercholesterolemia that affects ligand binding and intracellular movement of receptors.

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46.

Aalto-Setälä K et al. (1989) Finnish type of low density lipoprotein receptor gene mutation (FH-Helsinki) deletes exons encoding the carboxy-terminal part of the receptor and creates an internalization-defective phenotype.

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47.

Hobbs HH et al. (1989) Evidence for a dominant gene that suppresses hypercholesterolemia in a family with defective low density lipoprotein receptors.

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48.

Miyake Y et al. (1989) Analysis of a recycling-impaired mutant of low density lipoprotein receptor in familial hypercholesterolemia.

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49.

Ma YH et al. (1989) Identification of a second "French Canadian" LDL receptor gene deletion and development of a rapid method to detect both deletions.

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50.

Kajinami K et al. () New variant of low density lipoprotein receptor gene. FH-Tonami.

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51.

Langlois S et al. (1988) Characterization of six partial deletions in the low-density-lipoprotein (LDL) receptor gene causing familial hypercholesterolemia (FH).

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52.

Brink PA et al. (1987) Familial hypercholesterolemia in South African Afrikaners. PvuII and StuI DNA polymorphisms in the LDL-receptor gene consistent with a predominating founder gene effect.

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53.

Yamakawa K et al. (1988) TaqI polymorphism in the LDL receptor gene and a TaqI 1.5-kb band associated with familial hypercholesterolemia.

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54.

Esser V et al. (1988) Transport-deficient mutations in the low density lipoprotein receptor. Alterations in the cysteine-rich and cysteine-poor regions of the protein block intracellular transport.

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55.

Steyn K et al. (1989) The use of low density lipoprotein receptor activity of lymphocytes to determine the prevalence of familial hypercholesterolaemia in a rural South African community.

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56.

Knight BL et al. (1989) Defective processing and binding of low-density lipoprotein receptors in fibroblasts from a familial hypercholesterolaemic subject.

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57.

Südhof TC et al. (1985) The LDL receptor gene: a mosaic of exons shared with different proteins.

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58.

Horsthemke B et al. (1985) Identification of a deletion in the low density lipoprotein (LDL) receptor gene in a patient with familial hypercholesterolaemia.

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59.

Hobbs HH et al. (1985) Polymorphism and evolution of Alu sequences in the human low density lipoprotein receptor gene.

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60.

Lehrman MA et al. (1986) Exon-Alu recombination deletes 5 kilobases from the low density lipoprotein receptor gene, producing a null phenotype in familial hypercholesterolemia.

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61.

Hobbs HH et al. (1986) Deletion of exon encoding cysteine-rich repeat of low density lipoprotein receptor alters its binding specificity in a subject with familial hypercholesterolemia.

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62.

Slagel V et al. (1987) Clustering and subfamily relationships of the Alu family in the human genome.

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63.

Lehrman MA et al. (1985) Mutation in LDL receptor: Alu-Alu recombination deletes exons encoding transmembrane and cytoplasmic domains.

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64.

Henderson HE et al. (1988) A new LDL receptor gene deletion mutation in the South African population.

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65.

Leitersdorf E et al. (1988) Deletion in the first cysteine-rich repeat of low density lipoprotein receptor impairs its transport but not lipoprotein binding in fibroblasts from a subject with familial hypercholesterolemia.

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66.

Hobbs HH et al. (1988) Multiple crm- mutations in familial hypercholesterolemia. Evidence for 13 alleles, including four deletions.

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67.

Li HH et al. (1988) Amplification and analysis of DNA sequences in single human sperm and diploid cells.

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68.

Komuro I et al. (1987) The longest-lived patient with homozygous familial hypercholesterolemia secondary to a defect in internalization of the LDL receptor.

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69.

Kotze MJ et al. (1987) Haplotype associations of three DNA polymorphisms at the human low density lipoprotein receptor gene locus in familial hypercholesterolaemia.

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70.

Russell DW et al. (1986) The LDL receptor in familial hypercholesterolemia: use of human mutations to dissect a membrane protein.

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71.

Horsthemke B et al. (1987) Unequal crossing-over between two alu-repetitive DNA sequences in the low-density-lipoprotein-receptor gene. A possible mechanism for the defect in a patient with familial hypercholesterolaemia.

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72.

Horsthemke B et al. (1987) Identification of deletions in the human low density lipoprotein receptor gene.

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73.

Hobbs HH et al. (1987) Deletion in the gene for the low-density-lipoprotein receptor in a majority of French Canadians with familial hypercholesterolemia.

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74.

Lehrman MA et al. (1987) Duplication of seven exons in LDL receptor gene caused by Alu-Alu recombination in a subject with familial hypercholesterolemia.

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75.

Lehrman MA et al. (1987) Alu-Alu recombination deletes splice acceptor sites and produces secreted low density lipoprotein receptor in a subject with familial hypercholesterolemia.

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76.

Südhof TC et al. (1985) Cassette of eight exons shared by genes for LDL receptor and EGF precursor.

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77.

Lehrman MA et al. (1985) Internalization-defective LDL receptors produced by genes with nonsense and frameshift mutations that truncate the cytoplasmic domain.

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78.

Davis CG et al. (1986) The J.D. mutation in familial hypercholesterolemia: amino acid substitution in cytoplasmic domain impedes internalization of LDL receptors.

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79.

None (1985) Genes-in-pieces revisited.

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80.

Brown MS et al. (1974) Familial hypercholesterolemia: defective binding of lipoproteins to cultured fibroblasts associated with impaired regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity.

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81.

Goldstein JL et al. (1973) Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia.

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82.

Kingsley DM et al. (1984) Receptor-mediated endocytosis of low density lipoprotein: somatic cell mutants define multiple genes required for expression of surface-receptor activity.

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83.

Yamamoto T et al. (1984) The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA.

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84.

Torrington M et al. (1981) Familial hypercholesterolaemia and church affiliation.

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85.

Ullu E et al. () Alu sequences are processed 7SL RNA genes.

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86.

Tolleshaug H et al. (1982) Posttranslational processing of the LDL receptor and its genetic disruption in familial hypercholesterolemia.

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87.

Francke U et al. (1984) Assignment of the human gene for the low density lipoprotein receptor to chromosome 19: synteny of a receptor, a ligand, and a genetic disease.

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88.

Russell DW et al. (1984) Domain map of the LDL receptor: sequence homology with the epidermal growth factor precursor.

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89.

Allen JM et al. (1980) Cadiovascular complications of homozygous familial hypercholesterolaemia.

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90.

Seftel HC et al. (1980) A host of hypercholesterolaemic homozygotes in South Africa.

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91.

Koivisto UM et al. (1995) Molecular characterization of minor gene rearrangements in Finnish patients with heterozygous familial hypercholesterolemia: identification of two common missense mutations (Gly823>Asp and Leu380>His) and eight rare mutations of the LDL receptor gene.

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92.

Kotze MJ et al. (1995) A de novo duplication in the low density lipoprotein receptor gene.

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93.

Schuster H et al. (1995) Identification of the valine 408 to methionine mutation in the LDL receptor in a Greek patient with homozygous familial hypercholesterolemia.

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94.

Leren TP et al. (1994) Two founder mutations in the LDL receptor gene in Norwegian familial hypercholesterolemia subjects.

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95.

Sun XM et al. (1995) Characterization of a splice-site mutation in the gene for the LDL receptor associated with an unpredictably severe clinical phenotype in English patients with heterozygous FH.

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96.

Defesche JC et al. (1993) South African founder mutations in the low-density lipoprotein receptor gene causing familial hypercholesterolemia in the Dutch population.

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97.

Grossman M et al. (1994) Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia.

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98.

Schuster H et al. (1993) Identification of the serine-156 to leucine mutation in the low-density lipoprotein receptor in a German family with familial hypercholesterolemia.

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99.

Moorjani S et al. (1993) Mutations of low-density-lipoprotein-receptor gene, variation in plasma cholesterol, and expression of coronary heart disease in homozygous familial hypercholesterolaemia.

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100.

Savov A et al. (1995) Double mutant alleles: are they rare?

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101.

Feussner G et al. (1996) Unusual xanthomas in a young patient with heterozygous familial hypercholesterolemia and type III hyperlipoproteinemia.

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102.

Jensen HK et al. (1997) Two mutations in the same low-density lipoprotein receptor allele act in synergy to reduce receptor function in heterozygous familial hypercholesterolemia.

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103.

Gudnason V et al. (1997) Common founder mutation in the LDL receptor gene causing familial hypercholesterolaemia in the Icelandic population.

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104.

Vuorio AF et al. (1997) Familial hypercholesterolemia in the Finnish north Karelia. A molecular, clinical, and genealogical study.

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105.

Vergopoulos A et al. () A xanthomatosis-susceptibility gene may exist in a Syrian family with familial hypercholesterolemia.

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106.

Wilson DJ et al. (1998) A World Wide Web site for low-density lipoprotein receptor gene mutations in familial hypercholesterolemia: sequence-based, tabular, and direct submission data handling.

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107.

Lee WK et al. (1998) Identification of a common low density lipoprotein receptor mutation (C163Y) in the west of Scotland.

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108.

Mandelshtam M et al. (1998) Prevalence of Lithuanian mutation among St. Petersburg Jews with familial hypercholesterolemia.

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109.

Defesche JC et al. (1998) Molecular epidemiology of familial hypercholesterolaemia.

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110.

Ekström U et al. (1999) An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F).

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111.

Agnello V et al. (1999) Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor.

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112.

Knoblauch H et al. (2000) A cholesterol-lowering gene maps to chromosome 13q.

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113.

Thiart R et al. (2000) Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia.

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114.

Jensen JM et al. (1999) Linking genotype to aorto-coronary atherosclerosis: a model using familial hypercholesterolemia and aorto-coronary calcification.

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115.

Takahashi M et al. (2001) A novel mutation in exon 2 of the low-density lipoprotein-receptor gene in a patient with homozygous familial hypercholesterolemia.

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116.

Durst R et al. (2001) Recent origin and spread of a common Lithuanian mutation, G197del LDLR, causing familial hypercholesterolemia: positive selection is not always necessary to account for disease incidence among Ashkenazi Jews.

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117.

Koivisto UM et al. (2001) A novel cellular phenotype for familial hypercholesterolemia due to a defect in polarized targeting of LDL receptor.

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118.

Vergotine J et al. (2001) Prenatal diagnosis of familial hypercholesterolemia: importance of DNA analysis in the high-risk South African population.

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119.

Pisciotta L et al. (2002) A "de novo" mutation of the LDL-receptor gene as the cause of familial hypercholesterolemia.

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120.

Amsellem S et al. (2002) Intronic mutations outside of Alu-repeat-rich domains of the LDL receptor gene are a cause of familial hypercholesterolemia.

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121.

Rudenko G et al. (2002) Structure of the LDL receptor extracellular domain at endosomal pH.

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122.

None (1964) THE INHERITANCE OF ESSENTIAL FAMILIAL HYPERCHOLESTEROLEMIA.

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123.

Dedoussis GV et al. (2003) FH-Pyrgos: a novel mutation in the promoter (-45delT) of the low-density lipoprotein receptor gene associated with familial hypercholesterolemia.

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124.

Sato K et al. (2004) Soluble epoxide hydrolase variant (Glu287Arg) modifies plasma total cholesterol and triglyceride phenotype in familial hypercholesterolemia: intrafamilial association study in an eight-generation hyperlipidemic kindred.

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125.

Simard LR et al. (2004) The Delta>15 Kb deletion French Canadian founder mutation in familial hypercholesterolemia: rapid polymerase chain reaction-based diagnostic assay and prevalence in Quebec.

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126.

Bourbon M et al. (2007) A rare polymorphism in the low density lipoprotein (LDL) gene that affects mRNA splicing.

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127.

Lo JC et al. (2007) Lymphotoxin beta receptor-dependent control of lipid homeostasis.

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128.

Johansson F et al. (2008) Type 1 diabetes promotes disruption of advanced atherosclerotic lesions in LDL receptor-deficient mice.

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129.

Defesche JC et al. (2008) Silent exonic mutations in the low-density lipoprotein receptor gene that cause familial hypercholesterolemia by affecting mRNA splicing.

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130.

Zelcer N et al. (2009) LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor.

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131.

Huijgen R et al. (2010) Functionality of sequence variants in the genes coding for the low-density lipoprotein receptor and apolipoprotein B in individuals with inherited hypercholesterolemia.

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132.

Kulseth MA et al. (2010) Analysis of LDLR mRNA in patients with familial hypercholesterolemia revealed a novel mutation in intron 14, which activates a cryptic splice site.

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133.

Do R et al. (2015) Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction.

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