Large Intron Inversions in Romanian Patients with Hemophilia A—First Report
Melen Brinza,
Andra Grigore,
Mihaela Dragomir,
Dumitru Jardan,
Cerasela Jardan,
Paul Balanescu,
Claudia Cristina Tarniceriu,
Oana Viola Badulescu,
Cristina Blag,
Ciprian Tomuleasa,
Adina Traila,
Margit Serban,
Daniel Coriu
Affiliations
Melen Brinza
Department of Hematology and Bone Marrow Transplant, Fundeni Clinical Institute, 022328 Bucharest, Romania
Andra Grigore
Department of Hematology and Bone Marrow Transplant, Fundeni Clinical Institute, 022328 Bucharest, Romania
Mihaela Dragomir
Department of Hematology and Bone Marrow Transplant, Fundeni Clinical Institute, 022328 Bucharest, Romania
Dumitru Jardan
Molecular Biology Laboratory, Medlife, 010093 Bucharest, Romania
Cerasela Jardan
Department of Hematology and Bone Marrow Transplant, Fundeni Clinical Institute, 022328 Bucharest, Romania
Paul Balanescu
Internal Medicine Chair, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
Claudia Cristina Tarniceriu
Department of Anatomy, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
Oana Viola Badulescu
Department of Pathophysiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
Cristina Blag
Pediatric Discipline, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400177 Cluj Napoca, Romania
Ciprian Tomuleasa
Department of Hematology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj Napoca, Romania
Adina Traila
“Cristian Serban” Medical Center for Evaluation Therapy, Medical Education and Rehabilitation of Children and Young Adults, European Hemophilia Treatment Centre, 305100 Buzias, Romania
Margit Serban
Department of Onco-Hematology, “Louis Turcanu” Emergency Hospital for Children, 300011 Timisoara, Romania
Daniel Coriu
Department of Hematology and Bone Marrow Transplant, Fundeni Clinical Institute, 022328 Bucharest, Romania
Background and Objectives: Despite the vast heterogeneity in the genetic defects causing hemophilia A (HA), large intron inversions represent a major cause of disease, accounting for almost half of the cases of severe HA worldwide. We investigated the intron 22 and intron 1 inversion status in a cohort of Romanian unrelated patients with severe HA. Moreover, we evaluated the role of these inversions as relative risk factors in inhibitor occurrence. Materials and Methods: Inverse shifting—a polymerase chain reaction method was used to detect the presence of intron 22 and intron 1 inversions in 156 Romanian patients with HA. Results: Intron inversion 22 was found in 41.7% of the patients, while intron 1 inversion was detected in 3.2% of the patients. Overall, large intron inversions represented the molecular defect in 44.9% of the studied patients. Our findings are in accord with previously published reports from Eastern Europe countries and with other international studies. The risk of inhibitor development was higher in patients with inversion 1 compared to the patients with HA without any inversion detected. Conclusions: The current study demonstrates the major causative role of large intron inversions in severe HA in Romanian patients. Moreover, our study confirms the contribution of intron 1 inversion in inhibitor development.
