Universal screening for familial hypercholesterolemia in 2 populations |
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| Institution: | 1. Department of Endocrinology, Diabetes and Metabolism, University Children''s Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia;2. Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia;3. Children’s Hospital Auf der Bult, Janusz-Korczak-Allee, Hanover, Germany;4. Clinical Institute of Special Laboratory Diagnostics, University Children''s Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia;5. Unit Siska, Community Health Centre Ljubljana, Ljubljana, Slovenia;6. Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA;1. Department of Computer Science, Stanford University School of Engineering, Stanford, CA;2. Medical Scientist Training Program, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA;3. Department of Pediatrics, Stanford University School of Medicine, Stanford, CA;4. Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA;5. Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA;1. Human Genetics and Genetic Counseling Master''s Program, Stanford Medicine, Stanford, CA;2. Stanford Hospitals and Clinics Genetic Testing Optimization Service, Stanford Medicine, Stanford, CA;3. Department of Pathology, Stanford University, Stanford, CA;4. Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA;5. Quantitative Sciences Unit, Stanford University, Palo Alto, CA;1. Division of Pediatric Cardiology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX;2. Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, TX;3. Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School at Brown University, Providence, RI;4. Division of Vascular Surgery, Department of Surgery, University of Washington, Seattle, WA;5. Division of Medical Genetics, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center, Houston, TX;1. Ray D. Wolfe Department of Family Medicine, Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada;2. Department of Family & Community Medicine, University of Toronto, Ontario, Canada;3. C.T. Lamont Primary Health Care Research Centre, Bruyere Research Institute, Ottawa, Ontario, Canada;4. Department of Family Medicine, University of Ottawa, Ontario, Canada;5. Ontario eConsult Centre of Excellence, The Ottawa Hospital, Ottawa, Ontario, Canada;6. Ontario Health East, Ottawa, Ontario, Canada;7. Division of Endocrinology & Metabolism, The Ottawa Hospital, Ottawa, Ontario, Canada;8. Department of Medicine, University of Ottawa, Ontario, Canada;9. Laboratory Medicine and Genetics and Institute for Better Health, Trillium Health Partners, Mississauga, Ontario, Canada;10. Department of Laboratory Medicine & Pathobiology, University of Toronto, Ontario, Canada;11. Department of Pediatrics, University of Ottawa, Ontario, Canada;12. Department of Genetics, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada;13. Department of Family and Community Medicine, Women’s College Hospital, Toronto, Ontario, Canada;14. Department of Family Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada;15. Ontario Institute for Cancer Research, Toronto, Ontario, Canada;1. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN;2. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN;3. Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY;4. Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL;5. Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children’s Hospital Medical Center, Cincinnati, OH;6. Department of Medicine, Brigham and Women’s Hospital, Boston MA;7. Genomic Medicine Institute, Geisinger, Danville, PA;8. The Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA;9. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;10. Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA;11. Division of Pulmonary Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA;12. Division of Medical Genetics, Department of Medicine, University of Washington Medical Center, Seattle, WA;13. Department of Genome Sciences, University of Washington Medical Center, Seattle, WA;14. Department of Pediatrics, Columbia University Irving Medical Center, New York, NY;15. Department of Medicine, Columbia University Irving Medical Center, New York, NY;16. Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, MD;17. Gonda Vascular Center, Mayo Clinic, Rochester, MN |
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| Abstract: | PurposeIn Europe, >2 million individuals with familial hypercholesterolemia (FH) are currently undiagnosed. Effective screening strategies for FH diagnosis in childhood are urgently needed. We assessed the overall performances of 2 different FH screening programs in children: universal screening program with opt-out and opt-in type participation.MethodsWe analyzed the data from 2 independent populations based on >166,000 individuals screened for hypercholesterolemia. Genetic analyses of FH-related genes were finalized in 945 children and 99 parents.ResultsA total of 305 (32.3%) children were genotyped as positive or with a variant of uncertain significance in FH-related genes. For low-density lipoprotein cholesterol levels of 3.5 mmol L (135.3 mg/dL), the overall sensitivity and specificity for confirming FH were 90.5% and 55.3%, respectively. As part of child–parent screening, in >90% of the families, the parent with reported higher cholesterol levels was positive for the familial genetic variant. The cohort-based prevalence of FH from the opt-out universal screening program was estimated to be 1 in 431 individuals (95% CI = 1/391-1/472).ConclusionUniversal 3-step FH screening approach in children enabled detection of most children and their parents in every generation screened at reasonable costs. Opt-out screening strategy might be preferable over opt-in screening strategy. |
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| Keywords: | Children Cholesterol Familial hypercholesterolemia Genetic testing Universal screening |
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