Main Article Content

Yali Zhou
Guiping Liao
Xiaolin Yin
Sheng He
Yi Wu
Jian Xiao
Zhili Geng
Qiuying Huang
Ganghui Luo
Kun Yang


β-thalassemia; IVS-II-5 G>C; genotype; phenotype


Background: IVS-II-5 G>C (HBB: c.315+5 G>C) 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.

Methods: The clinical phenotypes associated with compound heterozygosity for the IVS-II-5 G>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.

Results: Next-generation sequencing of 24 undiagnosed patients with thalassemia major (TM) or thalassemia intermedia (TI) identified 13 carriers of the IVS-II-5 G>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 A2 levels at the same time.

Conclusion: Compound heterozygotes for IVS-II-5 G>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>C mutation can pose serious difficulties in screening and counseling.

Keywords: β-thalassemia; IVS-II-5 G>C; genotype; phenotype


Download data is not yet available.

Abstract 489
PDF Downloads 336
HTML Downloads 150


1. Michlitsch J, Azimi M, Hoppe C, Walters MC, Lubin B, Lorey F, et al. Newborn screening for hemoglobinopathies in California. Pediatr Blood Cancer. 2009;52(4):486-90.
2. Weatherall DJ. Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias. Nat Rev Genet. 2001;2(4):245-55.
3. Higgs DR. The molecular basis of α-thalassemia. Cold Spring Harb Perspect Med. 2013;3(1):a011718.
4. Jiang NH, Liang S, Su C, Nechtman JF, Stoming TA. A novel beta-thalassemia mutation [IVS-II-5 (G-->C)] in a Chinese family from Guangxi Province, P.R. China. Hemoglobin. 1993;17(6):563-7.
5. Zhao L, Qing J, Liang Y, Chen Z. A novel compound heterozygosity in Southern China: IVS-II-5 (G > C) and IVS-II-672 (A > C). Hemoglobin. 2016;40(6):428-30.
6. Shang X, Peng Z, Ye Y, Asan, Zhang X, Chen Y, et al. Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies. EBioMedicine. 2017;23:150-9.
7. Xiong F, Sun M, Zhang X, Cai R, Zhou Y, Lou J, et al. Molecular epidemiological survey of haemoglobinopathies in the Guangxi Zhuang Autonomous Region of southern China. Clin Genet. 2010;78(2):139-48.
8. He S, Qin Q, Yi S, Wei Y, Lin L, Chen S, et al. Prevalence and genetic analysis of α- and β-thalassemia in Baise region, a multi-ethnic region in southern China. Gene. 2017;619:71-5.
9. He S, Li J, Li DM, Yi S, Lu X, Luo Y, et al. Molecular characterization of α- and β-thalassemia in the Yulin region of Southern China. Gene. 2018;655:61-4.
10. Huang H, Xu L, Chen M, Lin N, Xue H, Chen L, et al. Molecular characterization of thalassemia and hemoglobinopathy in Southeastern China. Sci Rep. 2019;9(1):3493.
11. Jiang NH, Liang S. The beta+-thalassemia mutation [IVS-II-5 (G-->C] creates an alternative splicing site in the second intervening sequence. Hemoglobin. 1999;23(2):171-6.
12. Al-Salem AH, Nasserulla Z. Splenectomy for children with thalassemia. Int Surg. 2002;87(4):269-73.
13. Liao C, Mo QH, Li J, Li LY, Huang YN, Hua L, et al. Carrier screening for alpha- and beta-thalassemia in pregnancy: the results of an 11-year prospective program in Guangzhou Maternal and Neonatal hospital. Prenat Diagn. 2005;25(2):163-71.