Türk Dislipidemi Hastalarında Hiperlipidemi İlişkili Gen Paneli Kullanılarak Genotip ve Fenotip Analizi Yapılması

Amaç: Ailesel hiperkolesterolemi (AH), monogenik kalıtılan hastalıklardan en sık görülenlerden biridir. Çok sayıda gen ailesel hiperkolesterolemi ile ilişkilendirilmiştir ve ailesel hiperkolesterolemili hastalarda gen paneli testi ile araştırılmaktadır. Gereç ve Yöntem: Bu çalışmada, AH'li 28 hasta ve bir kısmının ebeveynleri, 32 genden oluşan hedeflenmiş bir panel kullanılarak yeni nesil dizileme (NGS) ile değerlendirildi. Bulgular: Altı hastada LDLR LIPC ve CETP genlerinde patojenik veya olası patojenik varyantlar tespit edildi. Sonuç: Klinik bulgular literatür ile karşılaştırılarak bu varyantların genotip-fenotip korelasyonları tartışıldı. Anahtar sözcükler: ailevi hiperlipidemi; LDLR; gen paneli dizileme testi

Anahtar Kelimeler:

ailevi hiperlipidemi, LDLR, gen paneli dizileme testi

Genotype and Phenotype Analysis Using a Hyperlipidemia-Associated Gene Panel in Turkish Dyslipidemia Patients

Objective: Familial hypercholesterolemia (FH) is one of the most frequent diseases with monogenic inheritance. Numerous genes have been associated with familial hypercholesterolemia and are being investigated by gene panel testing in patients with familial hypercholesterolemia. Methods: In the present study, 28 patients with FH and some of their parents were evaluated via next-generation sequencing (NGS) using a targeted panel of 32 genes. Results: Pathogenic or likely pathogenic variants were detected in six patients in the genes LDLR LIPC and CETP. Conclusion: The genotype-phenotype correlations of these variants were discussed by comparing the clinical findings with the literature.

Keywords:

familial hyperlipidemia, LDLR, gene panel sequencing test,

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1.https://reader.elsevier.com/reader/sd/pii/S0140673603142341?token=AF3D34AF95AF070560AD9B163FAEBD417AF0C3C225FFCE3176729 108EB7E06EEB35EF4F2FB66B83CABE2024413327642&originRegion=eu-west-1&originCreation=20220404122724, (accessed 04.04.2022)
2. Awan Z, Choi HY, Stitziel N, Ruel I, Bamimore MA, Husa R, et al. APOE p.Leu167del mutation in familial hypercholesterolemia. Atherosclerosis. 2013;231(2):218–22.
3. Veerkamp MJ, de Graaf J, Bredie SJH, Hendriks JCM, Demacker PNM, Stalenhoef AFH. Diagnosis of Familial Combined Hyperlipidemia Based on Lipid Phenotype Expression in 32 Families. Arteriosclerosis, Thrombosis, and Vascular Biology, 2002,22(2),274–82.
4. Khera AV, Won HH, Peloso GM, Lawson KS, Bartz TM, Deng X, et al. Diagnostic Yield of Sequencing Familial Hypercholesterolemia Genes in Severe Hypercholesterolemia. Journal of the American College of Cardiology. 2016, 7,67(22),2578–89.
5. Youngblom E, Pariani M, Knowles JW. Familial Hypercholesterolemia. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, et al., editors. GeneReviews® 1993 [cited 2022 Jun 24]. http://www.ncbi.nlm.nih.gov/books/NBK174884/
6. Cuchel M, Bruckert E, Ginsberg HN, Raal FJ, Santos RD, Hegele RA, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. European Heart Journal 2014,21,35(32),2146–57.
7. Bilgic GD, Genotype and Phenotype Analysis Using a Hypertrophic Cardiomyopathy-Associated Gene Panel in Turkish Cardiomyopathy Patients. Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi,2022, 9(2), 268-272.
8. Schuster H, Fischer HJ, Keller C, Wolfram G, Zöllner N. Identification of the 408 valine to methionine mutation in the low density lipoprotein receptor in a German family with familial hypercholesterolemia. Human Genetics. 1993,91(3),287–9.
9. Defesche JC, van Diermen DE, Lansberg PJ, Lamping RJ, Reymer PWA, Hayden MR, et al. South African founder mutations in the low-density lipoprotein receptor gene causing familial hypercholesterolemia in the Dutch population. Human Genetics. 1993,1;92(6),567–70.
10. Carlson LA, Holmquist L, Nilsson-Ehle P. Deficiency of hepatic lipase activity in post-heparin plasma in familial hyper-alpha-triglyceridemia. Acta Medica Scandinavica. 1986,219(5),435–47.
11. Durstenfeld A, Ben-Zeev O, Reue K, Stahnke G, Doolittle MH. Molecular characterization of human hepatic lipase deficiency. In vitro expression of two naturally occurring mutations. Arteriosclerosis and Thrombosis: A Journal of Vascular Biology. 1994,14(3),381–5.
12. Hegele RA, Little JA, Vezina C, Maguire GF, Tu L, Wolever TS, et al. Hepatic lipase deficiency. Clinical, biochemical, and molecular genetic characteristics. Arteriosclerosis and Thrombosis: A Journal of Vascular Biology. 1993,13(5),720–8.
13. Breckenridge WC, Little JA, Steiner G, Chow A, Poapst M. Hypertriglyceridemia associated with deficiency of apolipoprotein C-II. The New England Journal of Medicine. 1978,8;298(23),1265–73.
14. Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW, et al. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. The New England Journal of Medicine. 2004,8,350(15),1505–15.
15. Zannis VI, Fotakis P, Koukos G, Kardassis D, Ehnholm C, Jauhiainen M, et al. HDL biogenesis, remodeling, and catabolism. Handbook of Experimental Pharmacology. 2015,224,53–111.
16. Kardassis D, Thymiakou E, Chroni A. Genetics and regulation of HDL metabolism. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2022,1,1867(1),159060.