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A novel SPTB mutation causes hereditary spherocytosis via loss-of-function of β-spectrin

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Abstract

Hereditary spherocytosis (HS) is the most frequently observed chronic non-immune hemolytic disorder caused by altered red cell membrane function. SPTB gene mutation is one of the most common causes of HS, but pathogenicity analyses and pathogenesis research on these mutations have not been widely conducted. In this study, a novel heterozygous mutation of the SPTB gene (c.1509_1518del; p.K503Nfs*67) was identified in a Chinese family with HS by whole-exome sequencing (WES) and was then confirmed by Sanger sequencing. Next, the pathogenicity and pathogenesis of this mutation were studied using peripheral blood. We found that this mutation disrupted the synthesis and localization of β-spectrin and weakened the interaction between β-spectrin and ankyrin, which may be caused by the nonsense-mediated mRNA degradation pathway. These changes lead to the transformation of discoid erythrocytes into spherocytes, resulting in hemolytic anemia. Therefore, we classified this novel mutation as a pathogenic mutation leading to loss-of-function of β-spectrin. It would be insightful to perform the same mutation test and to provide genetic counseling to other relatives of the proband. Our study increases the current understanding of the molecular mechanisms related to mutations in SPTB.

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All data used in this study are available from the corresponding authors for request.

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Acknowledgements

The authors are grateful to the proband and his family for their participation.

Funding

The study was supported by the Gansu Key Laboratory of Genetics Study of Hematopathy (20JR10RA714) and the internal fund from The First Hospital of Lanzhou University (ldyyn2018-69 and ldyyn2020-17).

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Author notes

  1. Shan Li and Ping Guo contributed equally to this work.

Authors and Affiliations

  1. The First School of Clinical Medicine, Lanzhou University, Gansu, China

    Shan Li, Leyuan Mi, Kewang Xi & Ting Liu

  2. Departments of Obstetrics and Gynecology, Zhangye People’s Hospital, Hexi University, Gansu, China

    Ping Guo

  3. Clinical Laboratory Center, Gansu Provincial Maternity and Child Care Hospital, Gansu, China

    Leyuan Mi

  4. Central Laboratory, The First Hospital of Lanzhou University, 1 Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu, China

    Xiaojing Chai, Li Lu & Juan Li

Authors
  1. Shan Li
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  2. Ping Guo
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  8. Juan Li
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Contributions

Shan Li, Leyuan Mi, Kewang Xi, and Ting Liu performed the research, analyzed the results, and wrote the manuscript. Ping Guo, Xiaojing Chai, Li Lu, and Juan Li designed the study and substantively revised the manuscript. In addition, they intermediated the communication with the proband and his family and conducted a follow-up of two patients. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Juan Li.

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Li, S., Guo, P., Mi, L. et al. A novel SPTB mutation causes hereditary spherocytosis via loss-of-function of β-spectrin. Ann Hematol 101, 731–738 (2022). https://doi.org/10.1007/s00277-022-04773-3

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  • DOI: https://doi.org/10.1007/s00277-022-04773-3

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