Application of next-generation sequencing in thalassemia screening: A systematic review and meta-analysis

Abstract

Objective: To evaluate the value of next-generation sequencing (NGS) in the prevention and management of thalassemia. Methods: A systematic search was performed in eight databases including China Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang database, PubMed, EMBASE, Web of Science, and Cochrane Library from the inception to 1 June 2022. Stata 17.0 and Review Manager 5.4 were used for the meta-analysis. Results: Nine studies containing 14 794 participants were included in the meta-analysis. Compared with the routine genetic testing (including Gap-PCR and reverse dot blot), NGS had higher detection rates in screening thalassemia (RR 1.22, 95% CI 1.13-1.31, P<0.01), particularly for the α-thalassaemia mutation carriers (RR 1.24, 95% CI 1.07-1.44, P<0.01). However, no significant difference was found in the screening of β-thalassemia (RR 1.10, 95% CI 0.99-1.23, P>0.05). Conclusions: Compared with routine genetic testing, NGS had a higher detection rate in general, particularly in the detection of α-thalassemia.

Keywords

Thalassaemia / Next-generation sequencing / Meta-analysis

References

[1] Muncie HL Jr., Campbell J. Alpha and beta thalassemia. Am Fam Physician 2009; 80(4):339-344.

[2] Tarım H, Öz F. Thalassemia major and associated psychosocial problems: A narrative review. Iran J Public Health 2022; 51(1):12-18.

[3] Yang Y, Zhang J. Research progress on thalassemia in southern China. Chinese J Exp Hematol 2017; 25(1):276-280.

[4] Wu Y, Han L, Chen X, He J, Fan X, Dai J, et al. Effects of thalassemia on pregnancy outcomes of women with gestational diabetes mellitus. J Obstet Gynaecol Res 2022; 48(5):1132-1140.

[5] Prathyusha K, Venkataswamy M, Goud KS, Ramanjaneyulu K, Saikrupa K. Thalassemia: A blood disorder, its cause, prevention and management. Res J Pharm Dosage Forms Technol 2019; 11(3):975-4377.

[6] Zhang J, Xie M, Peng Z, Zhou X, Zhao T, Jin C, et al. Five novel globin gene mutations identified in five Chinese families by next-generation sequencing. Mol Genet Genomic Med 2021; 9(12):e1835.

[7] Munkongdee T, Chen P, Winichagoon P, Fucharoen S, Paiboonsukwong K. Update in laboratory diagnosis of thalassemia. Front Mol Biosci 2020; 7:74.

[8] Lun M. Application of next generation sequencing in genetic screening of neonatal thalassemia. China Health Vision 2021; 14:3.

[9] Lou GX, Li L, Zhou Y, Li L. Application of high throughput sequencing technology in genetic screening of neonatal thalassemia. Clin Lab J 2020; 9(2):137-138.

[10] Ye JX. Application value of high-throughput sequencing technology in screening for thalassemia in pregnant women. Guangdong: Shantou University; 2019.

[11] Wang K, Dang Y, Li Z, Pu Y, He S. Clinical significance of screening thalassemia with high throughput sequencing. J Exp Hematol 2019; 27(4):1220-1226.

[12] Yang YH. Epidemiological analysis of thalassemia in Guizhou province by next-generation sequencing. Guizhou:Zunyi Medical University; 2019.

[13] He SZ, Pu Y, Su H, Cao J, Mo L. Results of genetic screening of thalassemia by NGS and routine screening. Med J Nat Defend Forces Southwest China 2018; 28(5):404-406.

[14] He J, Song W, Yang J, Lu S, Yuan Y, Guo J, et al. Next-generation sequencing improves thalassemia carrier screening among premarital adults in a high prevalence population: The Dai nationality, China. Genet Med 2017; 19(9):1022-1031.

[15] Yang Q. Evaluation of high-throughput molecular diagnostic techniques in thalassemia screenning. Guangdong: Guangdong Medical University; 2017.

[16] Song CL, Liu Z, Chen S, Liu D, Zhou C. The value of next generation sequencing for large-scale genetic testing of thalassemia. China Med Devices 2016; 31(S1):15.

[17] Akca T, Ozdemir GN, Aycicek A, Ozkaya G. Long-term results of splenectomy in transfusion-dependent thalassemia. J Pediatr Hematol Oncol 2022. doi: 10.1097/MPH.0000000000002468.

[18] Long J, Sun L, Gong F, Zhang C, Mao A, Lu Y, et al. Third-generation sequencing: A novel tool detects complex variants in the α-thalassemia gene. Gene 2022; 822:146332.

[19] Wang M, Zhang X, Zhao Y, Lu Z, Xiao M. Prevalence and genetic analysis of thalassemia in childbearing age population of Hainan, The Free Trade Island in Southern China. J Clin Lab Ana 2022; 36(3):e24260.

[20] Nabavian M, Cheraghi F, Shamsaei F, Tapak L, Tamaddoni A. The psychosocial challenges of mothers of children with thalassemia: A qualitative study. J Educ Health Promot 2022; 11:37.

[21] 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; 23:150-159.

[22] Chen DM, Ma S, Tang XL, Yang JY, Yang ZL. Diagnosis of the accurate genotype of HKαα carriers in patients with thalassemia using multiplex ligation-dependent probe amplification combined with nested polymerase chain reaction. Chin Med J 2020; 133(10):1175-1181.

[23] Liang C, Chen XY, Gao X, Chen HJ, Jin YX, Zhou Y, et al. Spectrum of thalassemia mutations in fetuses of Han and Li ethinicities in Hainan province, China. Asian Pac J Trop Med 2019; 12(12):537-544.

[24] Chen P, Yu X, Huang H, Zeng W, He X, Liu M, et al. Evaluation of Ion Torrent next-generation sequencing for thalassemia diagnosis. J Int Med Res 2020; 48(12):300060520967778.

[25] Achour A, Koopmann TT, Baas F, Harteveld CL. The evolving role of next-generation sequencing in screening and diagnosis of hemoglobinopathies. Front Physiol 2021; 12(2):686689.

[26] Tan M, Bai Y, Zhang X, Sun J, Huang C, Tian R, et al. Early genetic screening uncovered a high prevalence of thalassemia among 18 309 neonates in Guizhou, China. Clin Genet 2021; 99(5):704-712.

[27] Zhao J, Li J, Lai Q, Yu Y. Combined use of gap-PCR and next-generation sequencing improves thalassaemia carrier screening among premarital adults in China. J Clin Pathol 2020; 73(8):488-492.