Abstract Body (Do not enter title and authors here): Introduction
Primary dyslipidemias represent a heterogeneous group of inherited disorders characterized by abnormal plasma levels of lipoproteins. Among them, familial hypercholesterolemia (FH) is the most prevalent and clinically significant condition due to its strong association with premature atherosclerotic cardiovascular disease (CVD). FH is most commonly caused by pathogenic variants in the LDLR, APOB, or PCSK9 genes, which lead to impaired clearance of low-density lipoprotein cholesterol (LDL-C) from the bloodstream and result in markedly elevated LDL-C levels from birth. Early identification and treatment are crucial to reduce morbidity and mortality. Despite this, FH remains widely underdiagnosed and undertreated.
Research question
In response to this public health challenge, in 2015 we established the LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network) registry, a collaborative nationwide initiative designed to enhance the clinical and molecular diagnosis of genetic dyslipidemias in Italy, with a primary focus on FH.
Methods
The LIPIGEN is an observational, multicenter, retrospective and prospective study. To date, it involves 64 specialized lipid clinics distributed throughout Italy (Figure). Patients with suspected FH are primarily identified on a clinical basis, considering LDL-C levels, signs of long-term exposure to hypercholesterolemia (as xanthomas), personal anamnesis of premature cardiovascular events and family history of hypercholesterolemia or CVD. These patients are then referred for genetic testing to screen for pathogenic variants in the relevant candidate genes. The biochemical and clinical data are collected and entered into a centralized database.
Results
To date, data from more than 11,800 individuals with a clinical diagnosis of FH have been recorded in the LIPIGEN database. Genetic testing has been performed in 78% of these individuals. Among them, a pathogenic or likely pathogenic variant was identified in 67% of cases, confirming the high diagnostic yield of targeted genetic analysis in this population. The most frequently mutated gene was LDLR, which is consistent with global epidemiologic data.
Conclusion
The creation and implementation of the LIPIGEN network represents a significant advancement in the landscape of dyslipidemia care in Italy. By promoting standardized clinical evaluation and widespread access to genetic testing, the LIPIGEN facilitates earlier diagnosis and better-targeted therapy for individuals with FH.