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• W4293579145 abstract "Background and Aims : Familial hypercholesterolemia (FH) is a common inherited disorder of low-density lipoprotein (LDL) catabolism causing elevated LDL-cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease. FH is typically caused by deleterious variants of LDLR, APOB or PCSK9 genes and its prevalence is of about 1:300 in the general population. Aim of this study was the genetic characterization of suspected FH patients.Methods: From 2014 to 2019 we collected 186 subjects with suspected FH (122 index cases and 64 relatives, aged ³18 years) who were clinically examined at the Lipid Clinic and tested by Next Generation Sequencing for genes associated with FH (LDLR, APOB, PCSK9, APOE, LDLRAP1, ABCG5, ABCG8, LIPA, CYP27A1, MYLIP).Results: Overall, 107 subjects (54 index patients/53 relatives) resulted to be heterozygous carriers of pathogenic variants of LDLR (103, 96.3%), APOB (3, 2.8%), or PCSK9 (1, 0.9%) genes. Five (likely)pathogenic variants of LDLR were not reported previously. Three of these caused frameshift with the occurrence of a premature termination codon (Gln33Profs*17, Cys243Trpfs*12, Val365Argfs*20). The other two were missense variants (Pro608His, Ala684Asp), involving highly conserved amino acids, which were found to be deleterious by “in silico” analysis (REVEL score 0.962 and 0.817, respectively).Conclusions: Clinical and genetic identification of FH patients represents a challenging task in clinical practice. In the present study we report 5 novel LDLR variants. Three of them can be regarded as deleterious due to the formation of a truncated protein. Clinical phenotypes and “in silico” analysis suggested that novel missense mutations can also be considered pathogenic. Background and Aims : Familial hypercholesterolemia (FH) is a common inherited disorder of low-density lipoprotein (LDL) catabolism causing elevated LDL-cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease. FH is typically caused by deleterious variants of LDLR, APOB or PCSK9 genes and its prevalence is of about 1:300 in the general population. Aim of this study was the genetic characterization of suspected FH patients. Methods: From 2014 to 2019 we collected 186 subjects with suspected FH (122 index cases and 64 relatives, aged ³18 years) who were clinically examined at the Lipid Clinic and tested by Next Generation Sequencing for genes associated with FH (LDLR, APOB, PCSK9, APOE, LDLRAP1, ABCG5, ABCG8, LIPA, CYP27A1, MYLIP). Results: Overall, 107 subjects (54 index patients/53 relatives) resulted to be heterozygous carriers of pathogenic variants of LDLR (103, 96.3%), APOB (3, 2.8%), or PCSK9 (1, 0.9%) genes. Five (likely)pathogenic variants of LDLR were not reported previously. Three of these caused frameshift with the occurrence of a premature termination codon (Gln33Profs*17, Cys243Trpfs*12, Val365Argfs*20). The other two were missense variants (Pro608His, Ala684Asp), involving highly conserved amino acids, which were found to be deleterious by “in silico” analysis (REVEL score 0.962 and 0.817, respectively). Conclusions: Clinical and genetic identification of FH patients represents a challenging task in clinical practice. In the present study we report 5 novel LDLR variants. Three of them can be regarded as deleterious due to the formation of a truncated protein. Clinical phenotypes and “in silico” analysis suggested that novel missense mutations can also be considered pathogenic." @default.
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• W4293579145 date "2022-08-01" @default.
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• W4293579145 title "Novel pathogenic variants of the LDLR gene identified in putative FH subjects" @default.
• W4293579145 doi "https://doi.org/10.1016/j.atherosclerosis.2022.06.734" @default.
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