Clinical utility gene card for: Hyperlipoproteinemia, TYPE II

Kassner, Ursula; Wühle-Demuth, Marion; Missala, Isabelle; Humphries, Steve E.; Steinhagen‐Thiessen, Elisabeth; Demuth, Ilja

doi:10.1038/ejhg.2013.271

Cited by 11 publications

(9 citation statements)

References 23 publications

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“…2 Furthermore, mutations in three genes are known to cause FH: the LDL receptor gene (LDLR), the apolipoprotein B gene (APOB) and the proprotein convertase subtilisin/kexin 9 gene (PCSK9). [3][4][5] Mutations in the LDL receptor adapter protein 1 gene (LDLRAP1) cause a very rare autosomal-recessive (AR) form of the disease, that is, AR hypercholesterolemia with a FH-like clinical phenotype. 6 The majority of FH causing variants have been found in the LDLR gene with currently over 1900 reported sequence alterations (https://databases.lovd.nl/ shared/genes/LDLR).…”

Section: Introductionmentioning

confidence: 99%

Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia

et al. 2020

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Autosomal-dominant familial hypercholesterolemia (FH) is characterized by increased plasma concentrations of low-density lipoprotein cholesterol (LDL-C) and a substantial risk to develop cardiovascular disease. Causative mutations in three major genes are known: the LDL receptor gene (LDLR), the apolipoprotein B gene (APOB) and the proprotein convertase subtilisin/kexin 9 gene (PCSK9). We clinically characterized 336 patients suspected to have FH and screened them for disease causing mutations in LDLR, APOB, and PCSK9. We genotyped six single nucleotide polymorphisms (SNPs) to calculate a polygenic risk score for the patients and 1985 controls. The 117 patients had a causative variant in one of the analyzed genes. Most variants were found in the LDLR gene (84.9%) with 11 novel mutations. The mean polygenic risk score was significantly higher in FH mutation negative subjects than in FH mutation positive patients (P < .05) and healthy controls (P < .001), whereas the score of the two latter groups did not differ significantly. However, the score explained only about 3% of the baseline LDL-C variance. We verified the previously described clinical and genetic variability of FH for German hypercholesterolemic patients. Evaluation of a six-SNP polygenic score recently proposed for clinical use suggests that it is not a reliable tool to classify hypercholesterolemic patients. Ursula Kassner and Ilja Demuth contributed equally to this study.

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Section: Introductionmentioning

confidence: 99%

Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia

et al. 2020

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“…A negative genetic test does not automatically exclude FH if the DLCN score is high. In previous studies, when patients were classified on the basis of the DLCN score, 70% of "definite" FH patients were found to carry a pathogenic variant, only 29% of "probable" FH and 11% of "possible" FH patients were variant positive [19].…”

Section: First Dlcn Assessment and Genetic Test Prescriptionmentioning

confidence: 97%

A Belgian consensus strategy to identify familial hypercholesterolaemia in the coronary care unit and its subsequent cascade screening and treatment: BEL-FaHST (The BELgium Familial Hypercholesterolaemia STrategy)

et al. 2018

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the author's institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are

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“…One of the most common of these monogenic disorders is familial hypercholesterolemia (FH), an autosomal dominant atherosclerotic disease. Up to 1 in 200–500 individuals carry one abnormal gene associated with FH [ 5 , 6 ]. Worldwide, most individuals affected by FH have a single mutation (heterozygotic) in either the low density lipoprotein receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Up to 1 in 200–500 individuals carry one abnormal gene associated with FH [ 5 , 6 ]. Worldwide, most individuals affected by FH have a single mutation (heterozygotic) in either the low density lipoprotein receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes [ 5 ]. Homozygous FH is more rare and serious, with an estimated frequency of one in a million [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Screening for Familial Hypercholesterolemia in Children: What Can We Learn From Adult Screening Programs?

et al. 2015

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Familial hypercholesterolemia (FH), an autosomal dominant atherosclerotic disease, is a common monogenic subtype of cardiovascular disease. Patients with FH suffer an increased risk of early onset heart disease. Early identification of abnormally elevated cholesterol signpost clinicians to interventions that will significantly decrease risk of related morbidity and mortality. Cascade genetic testing can subsequently identify at-risk relatives. Accordingly, a number of screening approaches have been implemented for FH in countries including the UK and the Netherlands. However, incomplete identification of cases remains a challenge. Moreover, the potential for early intervention is now raising questions about the value of implementing universal cholesterol screening approaches that focus on children. In this report, we briefly discuss the potential benefit of such screening. Additionally, we submit that ever increasing genome technological capability will force a discussion of including genetic tests in these screening programs. We discuss the opportunities and challenges presented by such an approach. We close with recommendations that the success of such screening endeavors will rely on a better integrated practice model in public health genomics that bridges stakeholders including practitioners in primary care, clinical genetics and public health.

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Clinical utility gene card for: Hyperlipoproteinemia, TYPE II

Cited by 11 publications

References 23 publications

Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia

Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia

A Belgian consensus strategy to identify familial hypercholesterolaemia in the coronary care unit and its subsequent cascade screening and treatment: BEL-FaHST (The BELgium Familial Hypercholesterolaemia STrategy)

Screening for Familial Hypercholesterolemia in Children: What Can We Learn From Adult Screening Programs?

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