Noa Shefer Averbuch1,2, Orna Steinberg-Shemer1,2, Orly Dgany3, Tanya Krasnov3, Sharon Noy-Lotan3, Joanne Yacobovich1,2, Amir A Kuperman4,5, Antonis Kattamis6, Ayelet Ben Barak7, Batia Roth-Jelinek8, Evgeni Chubar9, Evelyn Shabad10, Gustavo Dufort11, Martin Ellis2,12, Ofir Wolach2,13, Idit Pazgal2,14, Abed Abu Quider15, Hagit Miskin16,17, Hannah Tamary1,2. 1. Schneider Children's Medical Center of Israel, Petach Tikva, Israel. 2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 3. Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Petach Tikva, Israel. 4. Blood Coagulation Service and Pediatric Hematology Clinic, Galilee Medical Center, Nahariya, Israel. 5. Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel. 6. First Department of Pediatrics, National & Kapodistrian University of Athens, Athens, Greece. 7. Pediatric Hematology/Oncology Department, Rambam Medical Center, Haifa, Israel. 8. Department of Hematology, Hadassah Medical Center, Jerusalem, Israel. 9. Blood Bank, HaEmek Medical Center, Afula, Israel. 10. Blood Bank, Carmel Medical Center, Haifa, Israel. 11. Pediatric Hemato-Oncology Department, Centro Hospitalario Pereira Rossell, Montevideo, Uruguay. 12. Hematology Institute, Meir Medical Center, Kfar Saba, Israel. 13. Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel. 14. Comprehensive Center of Thalassemia, Hemoglobinopathies & Rare Anemias, Institute of Hematology, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel. 15. Pediatric Hematology, Soroka University Medical Center, Ben-Gurion University, Beer Sheva, Israel. 16. Pediatric Hematology Unit, Shaare Zedek Medical Center, Jerusalem, Israel. 17. Faculty of Medicine, Hebrew University, Jerusalem, Israel.
Abstract
BACKGROUND: Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes involved in rare anemias and the similarities in the clinical presentation of the different syndromes. OBJECTIVE: We aimed to enhance the diagnosis of patients with congenital anemias by using targeted next-generation sequencing. METHODS: Genetic diagnosis was performed by gene capture followed by next-generation sequencing of 76 genes known to cause anemia syndromes. RESULTS: Genetic diagnosis was achieved in 13 out of 21 patients (62%). Six patients were diagnosed with pyruvate kinase deficiency, 4 with dehydrated hereditary stomatocytosis, 2 with sideroblastic anemia, and 1 with CDA type IV. Eight novel mutations were found. In 7 patients, the genetic diagnosis differed from the pretest presumed diagnosis. The mean lag time from presentation to diagnosis was over 13 years. CONCLUSIONS: Targeted next-generation sequencing led to an accurate diagnosis in over 60% of patients with rare anemias. These patients do not need further diagnostic workup. Earlier incorporation of this method into the workup of patients with congenital anemia may improve patients' care and enable genetic counseling.
BACKGROUND: Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes involved in rare anemias and the similarities in the clinical presentation of the different syndromes. OBJECTIVE: We aimed to enhance the diagnosis of patients with congenital anemias by using targeted next-generation sequencing. METHODS: Genetic diagnosis was performed by gene capture followed by next-generation sequencing of 76 genes known to cause anemia syndromes. RESULTS: Genetic diagnosis was achieved in 13 out of 21 patients (62%). Six patients were diagnosed with pyruvate kinase deficiency, 4 with dehydrated hereditary stomatocytosis, 2 with sideroblastic anemia, and 1 with CDA type IV. Eight novel mutations were found. In 7 patients, the genetic diagnosis differed from the pretest presumed diagnosis. The mean lag time from presentation to diagnosis was over 13 years. CONCLUSIONS: Targeted next-generation sequencing led to an accurate diagnosis in over 60% of patients with rare anemias. These patients do not need further diagnostic workup. Earlier incorporation of this method into the workup of patients with congenital anemia may improve patients' care and enable genetic counseling.
Authors: Amanda Buyan; Charles D Cox; Jonathan Barnoud; Jinyuan Li; Hannah S M Chan; Boris Martinac; Siewert J Marrink; Ben Corry Journal: Biophys J Date: 2020-09-02 Impact factor: 4.033
Authors: Roberta Russo; Roberta Marra; Barbara Eleni Rosato; Achille Iolascon; Immacolata Andolfo Journal: Front Physiol Date: 2020-12-22 Impact factor: 4.566