Genetics familial hypercholesterolemia

Sitosterolemia is a rare monogenic lipid disease characterized by the excessive uptake of phytosterols and their accumulation in blood and tissues. Clinically, it can present with hypercholesterolemia and xanthomas, often causing it to be misdiagnosed as familial hypercholesterolemia (FH). The diagnosis of sitosterolemia can easily be confirmed and distinguished from FH with a sterol profile and genetic investigations. Here, we report a sibship of 2 sisters with sitosterolemia initially misdiagnosed as FH. This case report illustrates the importance of considering rare conditions, such as sitosterolemia, as a differential diagnosis in patients with hypercholesterolemia, xanthomas, and hematologic anomalies...

We report a case of a patient diagnosed with homozygous familial hypercholesterolemia and progressive supravalvular aortic stenosis. Treatment with long-term low-density lipoprotein apheresis and management with novel lipid-lowering agents including an angiopoetin-like protein inhibitor led to significant low-density lipoprotein reduction. The case highlights the challenges in managing the manifestations of homozygous familial hypercholesterolemia.

BACKGROUND AND AIMS: Familial hypercholesterolemia is an underdiagnosed genetic metabolic condition limiting the clearance of low-density lipoprotein cholesterol and increasing lifetime risk of cardiovascular disease. Population genetic screening in unselected individuals could quickly identify cases of familial hypercholesterolemia and enable early prevention, but the economic impact of widespread screening on patients has not been studied. METHODS: We assessed the cost-effectiveness of population genetic screening for familial hypercholesterolemia in 20 and 35-year-old adults in the United States from the perspective of patients...

BACKGROUND: Familial hypercholesterolemia (FH) comprises high LDL-cholesterol (LDL-c) levels and high cardiovascular disease risk. In the absence of pathogenic variants in causative genes, a polygenic basis was hypothesized. METHODS: In a population of 418 patients (excluding homozygotes) with clinical suspicion of FH, the FH-causative genes and the regions of single nucleotide polymorphisms (SNPs) included in 12-SNP and 6-SNP scores were sequenced by next-generation sequencing, allowing for the detection of pathogenic variants (V+) in 220 patients...

Background : The assessment of the risk of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolemia (HeFH) is determined by conventional risk factors. However, factors modifying CVD, or risk modifiers, beyond conventional risk factors may inform their CVD risk assessment and the subsequent use of new therapies. This work identifies and characterises patients within a lipid clinic cohort with regards to conventional CVD risk factors and risk modifiers with a focus on those with HeFH...

BACKGROUND: The diagnosis of familial hypercholesterolemia (FH) in children is primarily based on main criteria including low-density lipoprotein cholesterol (LDL-C) levels, increased in the proband and relatives, and its inheritance. Two other relevant parameters are symptoms, rarely occurring in children, as rare are the FH homozygous patients, and the mutation detection of related genes. The latter allows the final diagnosis, although it is not commonly available. Moreover, the application of diagnostic scores, useful in adults, is poorly applied in children...

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a highly prevalent genetic disorder resulting in markedly elevated LDL cholesterol levels and premature coronary artery disease. FH underdiagnosis and undertreatment require novel detection methods. This study evaluated the effectiveness of using an LDL cholesterol cut-off ≥99.5th percentile (sex- and age-adjusted) to identify clinical and genetic FH, and investigated underutilization of genetic testing and undertreatment in FH patients...

BACKGROUND: Premature aortic involvement and comprehensive management strategies in familial hypercholesterolemia familial hypercholesterolemia (FH), a rare autosomal dominant genetic disorder, poses significant challenges due to its propensity for elevated low-density lipoprotein cholesterol, premature coronary heart disease, and vascular atherosclerosis. CASE PRESENTATION: Unraveling Cardiovascular Complexities: A Striking Familial Hypercholesterolemia. This case study delves into a remarkable instance of FH in a 16-year-old female who presented with chest pain and worsening dyspnea...

Population-based genomic screening may help diagnose individuals with disease-risk variants. Here, we perform a genome-first evaluation for nine disorders in 29,039 participants with linked exome sequences and electronic health records (EHRs). We identify 614 individuals with 303 pathogenic/likely pathogenic or predicted loss-of-function (P/LP/LoF) variants, yielding 644 observations; 487 observations (76%) lack a corresponding clinical diagnosis in the EHR. Upon further investigation, 75 clinically undiagnosed observations (15%) have evidence of symptomatic untreated disease, including familial hypercholesterolemia (3 of 6 [50%] undiagnosed observations with disease evidence) and breast cancer (23 of 106 [22%])...

PURPOSE OF REVIEW: Autosomal dominant hypercholesterolemia is a common cause of cardiovascular disease. In addition to the classic genes that cause hypercholesterolemia, LDLR, APOB and PCSK9, a new locus has emerged as a candidate to be the cause of this hyperlipidemia, the p.(Leu167del) mutation in the APOE gene. RECENT FINDINGS: Various studies have demonstrated the involvement of the p.(Leu167del) mutation in the APOE gene in hypercholesterolemia: Studies of family segregation, lipoprotein composition by ultracentrifugation and proteomic techniques, and functional studies of VLDL-carrying p...

Coronary artery ectasia (CAE), defined as a 1.5-fold or greater enlargement of a coronary artery segment compared to the adjacent normal coronary artery, is frequently associated with atherosclerotic coronary artery disease (CAD). Membrane-bound endothelin converting enzyme-1 (ECE-1) is involved in the maturation process of the most potent vasoconstrictor ET-1. Polymorphisms in the endothelin (ET) gene family have been shown associated with the development of atherosclerosis. This study aims to investigate the effects of rs213045 and rs2038089 polymorphisms in the ECE-1 gene which have been previously shown to be associated with atherosclerosis and hypertension (HT), in CAE patients...

The field of cancer genetics has evolved significantly over the past 30 years. Genetic testing has become less expensive and more comprehensive which has changed practice patterns. It is no longer necessary to restrict testing to those with the highest likelihood of testing positive. In addition, we have learned that the criteria developed to determine who has the highest likelihood of testing positive are neither sensitive nor specific. As a result, the field is moving from testing only the highest risk patients identified based on testing criteria to testing all cancer patients...

PURPOSE: Dyslipidemia plays a pivotal role in increasing cardiovascular risk. In clinical practice the misleading association between altered lipid profile and obesity is common, therefore genetically inherited dyslipidemias may not completely be addressed among patients with overweight. Thus, we aim to investigate the influence of overweight and obesity on the lipid phenotype in a cohort of patients with different forms of dyslipidemia. METHODS: A retrospective analysis was conducted on patients with dyslipidemia from 2015 to 2022...

Familial hypercholesterolemia is a common genetic disorder of autosomal inheritance associated with elevated LDL-cholesterol. It is estimated to affect 1:250 individuals in general population roughly estimated to be 5 million in India. The prevalence of FH is higher in young CAD patients (<55 years in men; <60 years in women). FH is underdiagnosed and undertreated. Screening during childhood and Cascade screening of family members of known FH patients is of utmost importance in order to prevent the burden of CAD...

BACKGROUND: Familial hypercholesterolemia (FH) is a heritable disorder affecting 1.3 million individuals in the USA. Eighty percent of people with FH are undiagnosed, particularly minoritized populations including Black or African American people, Asian or Asian American people, and women across racial groups. Family cascade screening is an evidence-based practice that can increase diagnosis and improve health outcomes but is rarely implemented in routine practice, representing an important care gap...

BACKGROUND: We aimed to describe the frequency and yield of genetic testing in supravalvar aortic stenosis (SVAS) following negative evaluation for Williams-Beuren syndrome (WS). METHODS AND RESULTS: This retrospective cohort study included patients with SVAS at our institution who had a negative evaluation for WS from May 1991 to September 2021. SVAS was defined as (1) peak supravalvar velocity of ≥2 meters/second, (2) sinotubular junction or ascending aortic Z score <-2...

BACKGROUND: Individuals with homozygous familial hypercholesterolemia (HoFH) have a severe clinical problem in their first decade of life, which is not usually present in heterozygous FH (HeFH) individuals. For this latter group of patients, FH diagnosis is mostly severely delayed with a significant increase in the risk of angina, myocardial infarction, peripheral artery disease, stroke, and cardiovascular and all-cause mortality. METHODS: This study used various bioinformatics tools to analyze microarray data and identify critical miRNAs and their target genes associated with FH and its severity...

PURPOSE OF REVIEW: This review provides an overview of genetic and non-genetic causes of premature coronary artery disease (pCAD). RECENT FINDINGS: pCAD refers to coronary artery disease (CAD) occurring before the age of 65 years in women and 55 years in men. Both genetic and non-genetic risk factors may contribute to the onset of pCAD. Recent advances in the genetic epidemiology of pCAD have revealed the importance of both monogenic and polygenic contributions to pCAD...

Low-density lipoprotein cholesterol (LDL-c) is both a therapeutic target and a risk factor for cardiovascular disease (CVD). MicroRNA (miRNA) have been shown to regulate cholesterol homeostasis, and miRNA in blood circulation have been linked to hypercholesterolemia. However, few studies to date have associated miRNA with phenotypes like LDL-c in a healthy population. To this end, we analyzed circulating miRNA in relation to LDL-c in a healthy cohort of 353 participants using two separate bioinformatic approaches...

Genetic testing is key in modern healthcare, particularly for monogenic disorders such as familial hypercholesterolemia. This Tohoku Medical Megabank Project study explored the impact of first-degree relatives' dyslipidemia history on individual responses to familial hypercholesterolemia genomic results. Involving 214 participants and using Japan's 3.5KJPN genome reference panel, the study assessed preferences and intentions regarding familial hypercholesterolemia genetic testing results. The data revealed a significant inclination among participants with a family history of dyslipidemia to share their genetic test results, with more than 80% of participants intending to share positive results with their partners and children and 98...