An Unexpected Finding of a Novel 21.9 kb Deletion (Heyuan deletion, β21.9kb) β-Thalassemia During HbA1c Measurements

作者：Han-Xian Liao, Liang Liang, Xingyuan Chen, Yu Zheng, Ying Huang, Youqiong Li · 发表于：Clinical Laboratory · 年份：2025 · DOI：10.7754/clin.lab.2024.241035 · 研究领域：Hemoglobinopathies and Related Disorders、Genomics and Rare Diseases、Glycogen Storage Diseases and Myoclonus

BACKGROUND: β-thalassemia is predominantly caused by point mutations in the β-globin gene, whereas large deletions occur less frequently. Here, we described a novel 21.9 kb deletion found in a patient with β-thalassemia dur-ing HbA1c measurements. METHODS: The proband was a 25-year-old female who came to the hospital with her husband for routine prenatal examinations. The hemoglobin A1c(HbA1c) was measured by high-performance liquid chromatography (HPLC). Hb analysis was performed by capillary electrophoresis (CE). Routine genetic analysis was carried out by PCR and reverse dot-blot (PCR-RDB) and Gap-PCR. Multiplex ligation-dependent probe amplification (MLPA) was used to screen the deletion in the β-globin chain. Based on the MLPA results, the break location of the deletion was determined by third-generation sequencing (TGS). Sanger sequencing verified the breakpoint in the Gap-PCR amplification products of TGS. RESULTS: HbA1c measurements suggested an elevated HbF value (> 5%) by HPLC, and a retest of the Hb analysis showed an HbF value of 27.9%, and an Hb A2 value of 1.7% using CE. No mutations were detected by Gap-PCR and PCR-RDB. However, MLPA demostrated the presence of large fragment deletion in the β-globin chain. The positions of the deletion were located between 5,225,669 and 5,247,554 on chromosome 11 (chr11: 5,225,669-5,247,554; NG_000007.3:g.50,063-71,947 del) using TGS, spanning the length of 21,886 bp (21.9 kb deletion). CONCLUSIONS: This is the first report of...