Article Text

Combined use of gap-PCR and next-generation sequencing improves thalassaemia carrier screening among premarital adults in China
  1. Jianghong Zhao1,
  2. Jia Li2,
  3. Qiaohong Lai1,
  4. Yanping Yu1
  1. 1 Department of Obstetrics and Gynecology, Xiaolan Hospital Affiliated to Southern Medical University, Zhongshan, Guangdong province, China
  2. 2 Department of Thyroid and Breast, Shanghai Tenth People's Hospital, Shanghai, China
  1. Correspondence to Dr Jianghong Zhao, Department of Obstetrics and Gynecology, Southern Medical University, Zhongshan, Guangdong province, China; huangbuoying{at}163.com; Dr Yanping Yu, Department of Obstetrics and Gynecology, Xiaolan Hospital Affiliated to Southern Medical University, Zhongshan, Guangdong province, China; hbjmsr{at}163.com

Abstract

Aims Thalassaemia is one of the most common genetics disorders in the world, especially in southern China. The aim of the present study was to investigate the feasibility of combining the gap-PCR and next-generation sequencing (NGS) for thalassaemia carrier screening in the Chinese population.

Methods Blood samples were obtained from 944 prepregnancy couples; thalassaemia carrier screening was performed by using a routine haematological method and a combination of gap-PCR and NGS method.

Results We found that the α thalassaemia carrier rate was 11% (207/1888); the β thalassaemia carrier rate was 3.7% (70/1888); the composite α thalassaemia and β thalassaemia carrier rate was 0.4% (8/1888). We also identified seven novel mutations, including HBA1: c.412A>G, −50 (G>A), HBB: c.*+129T>A, HBB: c.-64G>C, HBB: c.-180G>C, HBB: c.*+5G>A and HBB: c.-113A>G. By comparing the combined gap-PCR and NGS method, the MCV+MCH and HbA2 detection strategy showed a lower sensitivity of 61.05% (105/172) and a higher missed diagnosis ratio of 38.95% (67/172) for α thalassaemia mutations. The sensitivity was improved with the MCV+MCH and HbA2 detection screen when compared with MCV+MCH detection for β thalassaemia (98.51% vs 85.90%).

Conclusions Our study suggests the combined gap-PCR and NGS method is a cost-effective method for the thalassaemia carrier screening, particularly for the α thalassaemia mutation carriers.

  • diagnostic screening
  • haematology
  • genetics
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

View Full Text

Statistics from Altmetric.com

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Footnotes

  • Handling editor Mary Frances McMullin.

  • Contributors YY designed the study and wrote the article; JZ and QL performed routine thalassemia analysis; QL performed the specific gap-PCR amplification and the DNA sequencing; JL wrote the manuscript and provided technical support. All authors approved the final manuscript.

  • Funding This research was financially supported by Science and Technology Planning Project of Zhongshan (grant/award number 2017B1007).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the medical ethics committee of Xiaolan People's Hospital of Zhongshan (XLLL-2017-KY-001).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.