Genetic causes of monogenic familial hypercholesterolemia in the Greek population: Lessons,mistakes, and the way forward |
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| Affiliation: | 1. Division of Endocrinology and Diabetes, The Children''s Hospital of Philadelphia, Philadelphia, PA, USA;2. Nemours Cardiac Center, A. I. DuPont Hospital for Children, Wilmington, DE, USA;3. Division of Gastroenterology, Hepatology, and Nutrition, The Children''s Hospital of Philadelphia, Philadelphia, PA, USA;4. Division of Endocrinology and Diabetes, Center for Translational Science, Children''s National Health System, Washington, DC, USA;1. Fundación Hipercolesterolemia Familiar, Madrid, Spain;2. Department of Nutrition, Clínica Las Condes, Santiago de Chile, Chile;3. Department of Internal Medicine, Hospital Abente y Lago, A Coruña, Spain;4. Department of Endocrinology, Hospital Ramón y Cajal, Madrid, Spain;5. Department of Internal Medicine, IMIBIC, Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain;6. Department of Internal Medicine, Fundación Jiménez Díaz, Madrid, Spain;7. Department of Internal Medicine, Hospital de Mérida, Mérida, Spain;8. Department of Pediatric Nephrology, Hospital Vall d''Hebrón, Barcelona, Spain;9. Department of Endocrinology, Hospital Universitario de Lugo, Lugo, Spain;10. Department of Internal Medicine, Hospital Donostia, San Sebastian, Spain;11. Department of Pediatrics, Hospital Universitario, Salamanca, Spain;12. Department of Internal Medicine, Hospital Universitario, Salamanca, Spain;13. Department of Internal Medicine, Hospital de Bellvitge, Barcelona, Spain;14. Cardiology Department, Hospital Clínico San Carlos, Madrid, Spain;1. Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C;2. Division of Cardiology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C;3. Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C;1. Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil;2. Lipid Clinic, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil |
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| Abstract: | Familial hypercholesterolemia (FH) is a leading cause of premature atherosclerosis. Genetic defects in the LDLR, APOB and PCSK9 genes cause FH, and confirmation of a gene defect is essential for an indisputable diagnosis of the disease. FH is underdiagnosed and we aimed to revise the genetic defects that have been characterized in FH patients of Greek origin and define an effective, future strategy for genetic studies. A literature search was performed in MEDLINE and EMBASE on genetic studies with FH patients of Greek origin. To date, no APOB and PCSK9 mutations have been found in the Greek population. It must be noted however, that only a small number of patients has been screened for PCSK9 mutations. In total, 41 LDLR defects have been characterized, with 6 common mutations c.1646G>A (p.Gly546Asp), c.858C>A (p.Ser286Arg), c.81C>G (p.Cys27Trp), c.1285G>A (p.Val429Met), c.517T>C (p.Cys173Arg), and c.1775G>A (p.Gly592Glu) that account for >80% of all mutations. Due to geographic isolation, founder mutations exist in a subpopulation in North West Greece and the Greek Cypriot population but not in the general population. Genetic testing should focus primarily on LDLR, and subsequently on PCSK9 and APOB. The Greek population is genetically homogeneous, which allows for a quick molecular diagnosis of the disease. Cascade screening is feasible and will certainly facilitate the identification of additional patients. |
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| Keywords: | Familial hypercholesterolemia Genetics Greek Mutations |
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