Loading...
Projects / Programmes source: ARIS

IDENTIFICATION OF GENETIC CAUSES OF DYSLIPIDEMIAS IN CHILDREN AND ADOLESCENTS AND THEIR EARLY DETECTION WITH UNIVERSAL SCREENING PROGRAM

Research activity

Code Science Field Subfield
3.07.00  Medical sciences  Metabolic and hormonal disorders   

Code Science Field
3.02  Medical and Health Sciences  Clinical medicine 
Keywords
dyslipidemia, rare dyslipidemias, poligenic hypercholesterolemia, familial hypercholesterolemia, rare diseases, genetics, familial hypercholesterolemia screening
Evaluation (rules)
source: COBISS
Researchers (27)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  23435  PhD Magdalena Avbelj Stefanija  Human reproduction  Researcher  2020 - 2023  178 
2.  13023  PhD Tadej Battelino  Medical sciences  Researcher  2020 - 2023  1,255 
3.  13409  PhD Nataša Bratina  Human reproduction  Researcher  2020 - 2023  433 
4.  38769  Barbara Čugalj Kern  Metabolic and hormonal disorders  Junior researcher  2020 - 2023  14 
5.  53302  Vanja Čuk  Human reproduction  Researcher  2020 - 2023  22 
6.  15657  PhD Maruša Debeljak  Oncology  Researcher  2020 - 2023  250 
7.  34849  PhD Klemen Dovč  Metabolic and hormonal disorders  Researcher  2020 - 2023  163 
8.  34908  Ana Drole Torkar  Microbiology and immunology  Researcher  2020 - 2023  67 
9.  33868  PhD Urh Grošelj  Human reproduction  Head  2020 - 2023  487 
10.  28512  PhD Tinka Hovnik  Medical sciences  Researcher  2020 - 2023  107 
11.  35356  PhD Barbara Jenko Bizjan  Medical sciences  Researcher  2020 - 2023  77 
12.  32049  PhD Marko Kavčič  Oncology  Researcher  2020 - 2023  80 
13.  21358  PhD Primož Kotnik  Human reproduction  Researcher  2020 - 2023  247 
14.  32181  PhD Jernej Kovač  Medical sciences  Researcher  2020 - 2023  212 
15.  51510  Jasmina Luskovec    Technical associate  2020 - 2023 
16.  29097  Brigita Mali    Technical associate  2020 - 2023 
17.  52445  Ajda Mezek  Human reproduction  Researcher  2020 - 2023 
18.  35406  PhD Daša Perko  Human reproduction  Researcher  2020 - 2023  37 
19.  31306  Žiga Iztok Remec  Human reproduction  Researcher  2020 - 2023  43 
20.  14020  PhD Barbka Repič Lampret  Human reproduction  Researcher  2020 - 2023  162 
21.  37426  PhD Robert Šket  Human reproduction  Researcher  2020 - 2023  73 
22.  29976  Jasna Šuput Omladič  Medical sciences  Researcher  2020 - 2023  40 
23.  50622  PhD Urša Šuštar  Metabolic and hormonal disorders  Junior researcher  2020 - 2022  32 
24.  37490  PhD Tine Tesovnik  Human reproduction  Researcher  2020 - 2023  66 
25.  20253  PhD Katarina Trebušak Podkrajšek  Human reproduction  Researcher  2020 - 2023  409 
26.  53301  Blanka Ulaga  Human reproduction  Researcher  2020 - 2023  11 
27.  15440  PhD Mojca Žerjav Tanšek  Human reproduction  Researcher  2020 - 2023  318 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,981 
Abstract
Familial hypercholesterolemia (FH) is the most common life-threatening inherited metabolic disorder and is linked to three genes LDLR, APOB, and PCSK9. The incidence of FH is around 1/250, but over 90% of patients in the developed world are undiagnosed. FH is characterised by a markedly elevated level of LDL (low-density lipoprotein) cholesterol from birth onwards, and thus causing accelerated atherosclerosis leading to premature cardiovascular complications. According to the most recent data, a patient with undiagnosed FH loses an average of 16 years of life. Early diagnosis, ideally in the context of population screening, is crucial to reduce the risk of cardiovascular complications, as effective, safe and cost-effective treatment is available. In Slovenia, we detect FH by screening all 5-year-old children, thus detecting the majority of all patients in the population, which is currently the only such population screening program for FH globally. Indirectly, within the population screened for FH, we also detect individuals with marked polygenic hypercholesterolemia or rare dyslipidemias (hypocholesterolemia, lysosomal acid lipase deficiency, inherited elevation of Lipoprotein(a) (Lp (a)), etc.). Polygenic hypercholesterolemia is caused by changes (or combinations of changes) in more than 100 different genes, with more pronounced cases being expressed as early as childhood. Rare dyslipidemias are a genetically and clinically heterogeneous group of inherited metabolic disorders and dozens of causal genes are currently known. Causal changes in LDLR, APOB, and PCSK9 genes during genetic testing (and thus confirmed FH) are detected in only about 40% of patients with dyslipidemia referred for FH population screening (e.g., in 2018, about 150 children were referred for further genetic analysis and out of them 60 had confirmed FH). However, the genetic cause of the other subjects has not yet been clarified, so we want to extend their genetic characterisation and try to identify the genetic cause of their dyslipidemia. Two main objectives of the project are: (1) to find new genetic variants involved in dyslipidemia with advanced next-generation sequencing technology (NGS), which enables the analysis of multiple genes simultaneously and (2) to develop a method to enable the routine and cost-effective genetic analysis of polygenic causes of hypercholesterolemia (to determine »polygenic score«) and at same time to enable genetic analysis of wide spectrum of rare dyslipidemias (those with hyper- and hypo-cholesterolemia). The method will be subsequently implemented in the universal screening program for cholesterol to detect the patients with rare dyslipidemias where the early detection is feasible and beneficial for early treatment. Thus, we want to identify causative variants in known genes associated with hypercholesterolemia and other primary dyslipidemias and to look for changes in potential other, yet unknown causal genes. According to data from the literature, we will expand the existing panel of genes associated with hypercholesterolemia, with causal genes for the most important rare dyslipidemias (abetalipoproteinemia, hypobetalipoproteinemia, lysosomal acid lipase deficiency, primary hypertriglyceridemia, sitosterolemia, hypoalphalipoproteinemia, hyperchylomicronemia, inherited elevation of Lipoprotein(a), etc.). However, we expect that, despite a larger set of analyzed genes, we will still not explain the genetic status of all patients, therefore in individuals with prominent phenotypes we will attempt to identify a polygenic cause based on the results of previous genome-wide association studies (GWAS) and/or perform an additional Whole-exome sequencing (WES) or Whole genome sequencing (WGS) in selected patients to identify changes in potential other, yet unknown causal genes. Genetic variations of unknown significance will be further evaluated with commercially available expression models.
Views history
Favourite