TY - JOUR AU - Zhou, Yali AU - Liao, Guiping AU - Yin, Xiaolin AU - He, Sheng AU - Wu, Yi AU - Xiao, Jian AU - Geng, Zhili AU - Huang, Qiuying AU - Luo, Ganghui AU - Yang, Kun PY - 2022/04/28 Y2 - 2024/03/29 TI - THE CLINICAL SIGNIFICANCE OF THE SPECTRUM OF INTERACTIONS OF THE RARE IVS-II-5 G>C (HBB: C.315+5 G>C) VARIATION WITH OTHER Β-THALASSEMIA MUTATIONS IN SOUTHERN CHINA JF - Mediterranean Journal of Hematology and Infectious Diseases JA - Mediterr J Hematol Infect Dis VL - 14 IS - 1 SE - Original Articles DO - 10.4084/MJHID.2022.034 UR - https://www.mjhid.org/mjhid/article/view/4916 SP - e2022034 AB - <p><strong>Background:</strong> IVS-II-5 G&gt;C (<em>HBB: c.315+5 G&gt;C</em>) is a rare β-thalassemia mutation. However, there is no clear evidence regarding the effect of this defect or co-inheritance of other β-thalassemia mutations on phenotypes.</p><p><strong>Methods: </strong>The clinical phenotypes associated with compound heterozygosity for the IVS-II-5 G&gt;C mutation with other β-thalassemia mutations, together with the potential effect of the genetic modifiers α-thalassemia were studied in 13 patients. Analyses of red cell indices, hemoglobin component, iron status, and α-globin genes were carried out in 19 heterozygotes.</p><p><strong>Results: </strong>Next-generation sequencing of 24 undiagnosed patients with thalassemia major (TM) or thalassemia intermedia (TI) identified 13 carriers of the IVS-II-5 G&gt;C mutation. There was a wide spectrum of phenotypic severity in compound heterozygotes and 6 (46.2%) of 13 were transfusion dependent. Analysis of 19 heterozygotes indicated that most were hematologically normal without appreciable microcytosis or hypochromia, and approximately half had normal hemoglobin A<sub>2</sub> levels at the same time.</p><p><strong>Conclusion: </strong>Compound heterozygotes for IVS-II-5 G&gt;C and other severe β-thalassemia mutations are phenotypically severe enough to necessitate appropriate therapy and counseling. Co-inheritance of this nucleotide substitution with other β-thalassemia mutations may account for a considerable portion of the incidence of undiagnosed patients with TI and TM in Guangxi. The IVS-II-5 G&gt;C mutation can pose serious difficulties in screening and counseling.</p><p><strong>Keywords</strong>: β-thalassemia; IVS-II-5 G&gt;C; genotype; phenotype</p> ER -