Facile discovery of red blood cell deformation and compromised membrane/skeleton assembly in Prader–Willi syndrome

Abstract

Prader–Willi syndrome (PWS) is a rare congenital disease with genetic alterations in chromosome 15. Although genetic disorders and DNA methylation abnormalities involved in PWS have been investigated to a significant degree, other anomalies such as those in erythrocytes may occur and these have not been clearly elucidated. In the present study, we uncovered slight anemia in children with PWS that was associated with increased red blood cell (RBC) distribution width (RDW) and contrarily reduced hematocrit (HCT) values. Intriguingly, the increased ratio in RDW to HCT allowed sufficient differentiation between the PWS patients from the healthy controls and, importantly, with individuals exhibiting conventional obesity. Further morphologic examinations revealed a significant deformity in erythrocytes and mild hemolysis in PWS patients. Comprehensive mechanistic investigations unveiled compromised membrane skeletal assembly and membrane lipid composition, and revealed a reduced F-actin/G-actin ratio in PWS patients. We ascribed these phenotypic changes in erythrocytes to the observed genetic defects, including DNA methylation abnormalities. Our collective data allowed us to uncover RBC deformation in children with PWS, and this may constitute an auxiliary indicator of PWS in early childhood.

Keywords

Prader–Willi syndrome / early diagnosis / erythrocyte deformation / membrane skeleton / membrane lipid

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Acknowledgements

The authors would like to thank the National Natural Science Foundation of China (Nos. 81974124 and 22076104), the “Outstanding University Driven by Talents” Program and Academic Promotion Program of Shandong First Medical University (Nos. 2019LJ007 and 2020LJ002). We thank LetPub for its linguistic assistance during the preparation of this manuscript.

Compliance with ethics guidelines

Yashuang Yang, Guimei Li, Yanzhou Wang, Yan Sun, Chao Xu, Zhen Wei, Shuping Zhang, Ling Gao, Sijin Liu, and Jiajun Zhao declare that they have no conflict of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

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