MRI‐Based Iron Phenotyping and Patient Selection for Next‐Generation Sequencing of Non–Homeostatic Iron Regulator Hemochromatosis Genes
| العنوان: | MRI‐Based Iron Phenotyping and Patient Selection for Next‐Generation Sequencing of Non–Homeostatic Iron Regulator Hemochromatosis Genes |
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| المؤلفون: | Reinhard Stauder, Christian Kremser, Benjamin Henninger, Andreas R. Janecke, Andre Franke, Herbert Tilg, Marlene Panzer, André Viveiros, Marc P. Hoeppner, Benedikt Schaefer, Michaela Plaikner, Sören Franzenburg, Heinz Zoller |
| المصدر: | Hepatology (Baltimore, Md.) |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Genotype, Iron, Transferrin receptor, Chronic liver disease, Gastroenterology, Steatohepatitis/Metabolic Liver Disease, Hepcidin, Internal medicine, Receptors, Transferrin, medicine, Humans, Genetic Testing, Hemochromatosis Protein, Hemochromatosis, Aged, Retrospective Studies, Genetic testing, Hepatology, biology, medicine.diagnostic_test, business.industry, Transferrin saturation, Liver Diseases, Patient Selection, Homozygote, Ceruloplasmin, High-Throughput Nucleotide Sequencing, Original Articles, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Ferritin, Phenotype, Liver, Ferritins, Mutation, biology.protein, Female, Original Article, business, Follow-Up Studies |
| الوصف: | BACKGROUND AND AIMS High serum ferritin is frequent among patients with chronic liver disease and commonly associated with hepatic iron overload. Genetic causes of high liver iron include homozygosity for the p.Cys282Tyr variant in homeostatic iron regulator (HFE) and rare variants in non-HFE genes. The aims of the present study were to describe the landscape and frequency of mutations in hemochromatosis genes and determine whether patient selection by noninvasive hepatic iron quantification using MRI improves the diagnostic yield of next-generation sequencing (NGS) in patients with hyperferritinemia. APPROACH AND RESULTS A cohort of 410 unselected liver clinic patients with high serum ferritin (defined as ≥200 μg/L for women and ≥300 μg/L for men) was investigated by HFE genotyping and abdominal MRI R2*. Forty-one (10%) patients were homozygous for the p.Cys282Tyr variant in HFE. Of the remaining 369 patients, 256 (69%) had high transferrin saturation (TSAT; ≥45%) and 199 (53%) had confirmed hepatic iron overload (liver R2* ≥70 s-1 ). NGS of hemochromatosis genes was carried out in 180 patients with hepatic iron overload, and likely pathogenic variants were identified in 68 of 180 (38%) patients, mainly in HFE (79%), ceruloplasmin (25%), and transferrin receptor 2 (19%). Low spleen iron (R2* |
| تدمد: | 1527-3350 0270-9139 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a39bf4d7b87ae3cfa95b2afd78d5b5cTest https://doi.org/10.1002/hep.31982Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4a39bf4d7b87ae3cfa95b2afd78d5b5c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15273350 02709139 |
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