Advertisement

Optimization and application of a dried blood spot-based genetic screening method for thalassemia in Shenzhen newborns

  • Wei WenEmail author
  • Meng Guo
  • Hong-bing Peng
  • Li Ma
Brief Report
  • 28 Downloads

Abstract

Background

To optimize and apply an approach suitable for large-scale neonatal thalassemia genetic screening in China, thalassemia genotypes were determined by polymerase chain reaction-reverse dot blot using DNA extracted from dried blood spots (DBS) obtained from newborn screening programs.

Methods

Firstly, the most suitable commercial DNA extraction kit for DBS was screened. Then, the appropriate amount of DBS required for the automated high-throughput DNA extraction system was evaluated. Finally, the thalassemia prevalence and genotype spectrum in Shenzhen were investigated in 2028 newborns using the optimized screening procedure.

Results

The Magentec extraction kit was best suited for the automated DBS DNA extraction system using eight 3-mm DBS discs. The neonatal thalassemia prevalence in Shenzhen was 9.12%; 6.31% α-thalassemia, 2.37% β-thalassemia, and 0.44% α-/β-thalassemia.

Conclusions

Genetic screening based on DBS can precisely identify the thalassemia genotypes. Both α- and β-thalassemia are widely distributed in Shenzhen newborns. Newborn genetic screening is important for establishing a comprehensive thalassemia prevention program and for public education.

Keywords

Dried blood spot Genetic screening Newborn screening Thalassemia 

Notes

Author contributions

WW and MG designed the experiment, collected and analyzed the data, and wrote the manuscript. HBP and LM collected and analyzed the data. All authors have read and approved the final version of the manuscript.

Funding

None.

Compliance with ethical standards

Ethical approval

The study conducted in the Maternal and Child Health Hospital and was approved by the Medical Ethics Committee of the Maternal and Child Health Hospital of Shenzhen, Guangdong province, China.

Conflict of interest

None financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

References

  1. 1.
    Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386:743–800.Google Scholar
  2. 2.
    Kim S, Tridane A. Thalassemia in the United Arab Emirates: why it can be prevented but not eradicated. PLoS One. 2017;12:e0170485.CrossRefGoogle Scholar
  3. 3.
    Cao A, Galanello R, Rosatelli MC. Prenatal diagnosis and screening of the haemoglobinopathies. Baillieres Clin Haematol. 1998;11:215–38.CrossRefGoogle Scholar
  4. 4.
    Hang M, Iseman S. “Villages” in Shenzhen: typical economic phenomena of rural urbanization in China. Chin Sociol Anthropol. 2009;41:90–107.CrossRefGoogle Scholar
  5. 5.
    Brancaleoni V, Di Pierro E, Motta I, Cappellini MD. Laboratory diagnosis of thalassemia. Int J Lab Hematol. 2016;38(Suppl 1):32–40.CrossRefGoogle Scholar
  6. 6.
    Hannon W, Baily C, Bartoshesky L, Davin B, Hoffman G, King P, et al. Blood collection on filter paper for newborn screening programs; approved standard. Clin Lab Stand Inst. 2007;23:1–33.Google Scholar
  7. 7.
    Ryan K, Bain BJ, Worthington D, James J, Plews D, Mason A, et al. Significant haemoglobinopathies: guidelines for screening and diagnosis. Br J Haematol. 2010;149:35–49.CrossRefGoogle Scholar
  8. 8.
    Miri-Moghaddam E, Sargolzaie N. Cut off determination of discrimination indices in differential diagnosis between iron deficiency anemia and beta-thalassemia minor. Int J Hematol Oncol Stem Cell Res. 2014;8:27–32.Google Scholar
  9. 9.
    Denic S, Agarwal MM, Al Dabbagh B, El Essa A, Takala M, Showqi S, et al. Hemoglobin A2 lowered by iron deficiency and alpha-thalassemia: should screening recommendation for beta-thalassemia change? ISRN Hematol. 2013;2013:858294.CrossRefGoogle Scholar
  10. 10.
    Hariharan P, Colaco S, Colah R, Ghosh K, Nadkarni A. Delta globin gene variations leading to reduction in HbA2 levels. Int J Lab Hematol. 2016;38:610–5.CrossRefGoogle Scholar
  11. 11.
    Ng EH, Leung JH, Lau YS, Ma ES. Evaluation of the new red cell parameters on Beckman Coulter DxH800 in distinguishing iron deficiency anaemia from thalassaemia trait. Int J Lab Hematol. 2015;37:199–207.CrossRefGoogle Scholar
  12. 12.
    Mantikou E, Arkesteijn SG, van Beckhoven JM, Kerkhoffs JL, Harteveld CL, Giordano PC. A brief review on newborn screening methods for hemoglobinopathies and preliminary results selecting beta thalassemia carriers at birth by quantitative estimation of the HbA fraction. Clin Biochem. 2009;42:1780–5.CrossRefGoogle Scholar
  13. 13.
    Bowden D. Screening for thalassaemia. Aust Prescr. 2001;24:120–3.CrossRefGoogle Scholar
  14. 14.
    Li B, Zhang XZ, Yin AH, Zhao QG, Wu L, Ma YZ, et al. High prevalence of thalassemia in migrant populations in Guangdong Province, China. BMC Public Health. 2014;14:905.CrossRefGoogle Scholar
  15. 15.
    Lai K, Huang G, Su L, He Y. The prevalence of thalassemia in mainland China: evidence from epidemiological surveys. Sci Rep. 2017;7:920.CrossRefGoogle Scholar
  16. 16.
    Li CG, Li CF, Li Q, Li M. Thalassemia incidence and treatment in China with special reference to Shenzhen City and Guangdong province. Hemoglobin. 2009;33:296–303.CrossRefGoogle Scholar
  17. 17.
    Moghaddam ZK, Bayat N, Valaei A, Kordafshari A, Zarbakhsh B, Zeinali S, et al. Coinheritance of α-and β-thalassemia: challenges in prenatal diagnosis of thalassemia. Iran J Blood Cancer. 2012;2:81–4.CrossRefGoogle Scholar
  18. 18.
    Li J, Xie XM, Liao C, Li DZ. Co-inheritance of alpha-thalassaemia and beta-thalassaemia in a prenatal screening population in mainland China. J Med Screen. 2014;21:167–71.CrossRefGoogle Scholar

Copyright information

© Children's Hospital, Zhejiang University School of Medicine 2019

Authors and Affiliations

  1. 1.Neonatal Screening CenterShenzhen Maternity and Child Healthcare HospitalShenzhenChina

Personalised recommendations