Department of Hematology and Bone Marrow Transplant, Fundeni Clinical Institute, 022328 Bucharest, Romania.
Department of Hematology, "Carol Davila" University of Medicine and Pharmacy, 020021 Bucharest, Romania.
Medicina (Kaunas). 2023 Oct 13;59(10):1821. doi: 10.3390/medicina59101821.
: 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. : 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. : 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. : 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.
尽管导致血友病 A (HA) 的遗传缺陷存在很大的异质性，但大片段内含子倒位是疾病的主要原因，几乎占全球重度 HA 病例的一半。我们研究了罗马尼亚无亲缘关系的重度 HA 患者队列中的内含子 22 和内含子 1 倒位情况。此外，我们评估了这些倒位作为抑制剂发生的相对风险因素的作用。
采用反转录聚合酶链反应方法检测了 156 例罗马尼亚 HA 患者的内含子 22 和内含子 1 倒位情况。
结果发现，41.7%的患者存在内含子 22 倒位，3.2%的患者存在内含子 1 倒位。总体而言，44.9%的研究患者存在大片段内含子倒位。我们的发现与东欧国家和其他国际研究的先前发表的报告一致。与未检测到任何倒位的 HA 患者相比，1 号内含子倒位患者发生抑制剂的风险更高。
本研究表明，大片段内含子倒位是罗马尼亚重度 HA 患者的主要致病因素。此外，我们的研究证实了内含子 1 倒位在抑制剂发展中的作用。
