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Prader-Willi syndrome gene expression profiling of obese and non-obese patients reveals transcriptional changes in CLEC4D and ANXA3

  • Ju Young Yoon , Choong Ho Shin EMAIL logo , Murim Choi , Jung Min Ko , Young Ah Lee , Kye Shik Shim , Jun Lee , Suk Dong Yoo , Minji Kim , Yeuni Yu , Joo Young Lee , Yun Hak Kim ORCID logo and Chong Kun Cheon ORCID logo EMAIL logo
Published/Copyright: March 20, 2025
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 5

Abstract

Objectives

We aimed to characterize genetic alterations in Prader-Willi syndrome (PWS) using whole genome microarrays.

Methods

We performed mRNA expression microarray analysis using RNA isolated from whole blood of 25 PWS patients and 25 age-matched controls. After preprocessing the data to reduce heterogeneity, differentially expressed genes (DEGs) between groups were identified using a linear regression model package. Reactome pathway analysis was performed for upregulated and downregulated genes using EnrichR. Correlations between gene expression levels and clinical factors were estimated using Spearman’s rank correlation coefficient.

Results

Of 21,488 probes examined in the microarray analysis, 4,156 were detected. Fifty-two genes had different expression levels in children with PWS compared with healthy controls (36 genes upregulated and 16 downregulated). Twelve genes were upregulated and 13 were downregulated in obese PWS patients compared with normal-weight PWS (NW-PWS) patients. The C-type lectin domain family 4 member D (CLEC4D) was upregulated in both PWS (vs. control) and obese-PWS (vs. NW-PWS) patients, and CLEC4D expression was also correlated with body mass index-standard deviation score in PWS patients. Among the genes upregulated in obese PWS vs. NW-PWS, Annexin A3 (ANXA3), potassium inwardly rectifying channel subfamily J member 15 (KCNJ15), and selenium binding protein 1 (SELENBP1) were upregulated in obese-control vs. NW-control. Gene ontology analysis revealed that upregulated DEGs were significantly enriched in biological processes, including pathways involved in myeloid dendritic cell activation associated with CLEC4D.

Conclusions

This study revealed differences in gene expression between obese and NW-PWS patients. The regulation of macrophage infiltration by CLEC4D suggests a possible mechanism associated with obesity-related complications in PWS.

Keywords: Prader-Willi syndrome; mRNA; expression microarray; obesity; CLEC4D
Corresponding authors: Choong Ho Shin, Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Korea, E-mail: ; and Chong Kun Cheon, Department of Pediatrics, Pusan National University Children’s Hospital, Pusan National University School of Medicine, Geumo-ro 20, Yangsan 50612, Korea; and Medical Research Institute, Pusan National University, Pusan, Korea, E-mail:
Ju Young Yoon and Yeuni Yu contributed equally to this work.

Acknowledgments

This study was supported by the Research Institute for Convergence of biomedical science and technology (30-2021-005), Pusan National University Yangsan Hospital.

  1. Research ethics: The local Institutional Review Board deemed the study exempt from review.

  2. Informed consent: Informed consent was obtained from all individuals included in this study.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: Authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: Not applicable.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/jpem-2024-0408).

Received: 2024-08-23
Accepted: 2025-01-27
Published Online: 2025-03-20
Published in Print: 2025-05-26

© 2025 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. A recent update on childhood obesity: aetiology, treatment and complications
  4. Original Articles
  5. Chronotype, sleep, and glycemic control in children and adolescents with type 1 diabetes: a case-control study
  6. Determinants of childhood and adolescent obesity and it’s effect on metabolism in South Indian population
  7. Evaluation of continuous glucose monitoring and nutritional status in glycogen storage diseases
  8. Retrospective assessment of hepatic involvement in patients with inherited metabolic disorders: nine-year single-center experience
  9. Relationships among biological sex, body composition, and bone mineral density in young persons with and without diabetes
  10. The clinical characteristics of 10 cases and adult height of six cases of rare familial male-limited precocious puberty
  11. Optimal timing of repeat thyroid fine-needle aspiration biopsy
  12. Medium-chain acyl-CoA dehydrogenase deficiency in North Macedonia – ten years experience
  13. The effect of antenatal steroids on metabolic bone disease of prematurity
  14. Prader-Willi syndrome gene expression profiling of obese and non-obese patients reveals transcriptional changes in CLEC4D and ANXA3
  15. Early-onset growth hormone treatment in Prader–Willi syndrome attenuates transition to severe obesity
  16. Case Reports
  17. Neonatal severe hyperparathyroidism with inactivating calcium sensing receptor (CaSR) mutation (p.I81K)
  18. Clinical manifestations and molecular genetics of seven patients with Niemann–Pick type-C: a case series with a novel variant
  19. Expanding the genotypic spectrum of 3β-hydroxy-δ5-C27-steroid dehydrogenase (HSD3B7) deficiency: novel mutations and clinical outcomes
https://doi.org/10.1515/jpem-2024-0408
Keywords for this article
Prader-Willi syndrome; mRNA; expression microarray; obesity; CLEC4D

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. A recent update on childhood obesity: aetiology, treatment and complications
  4. Original Articles
  5. Chronotype, sleep, and glycemic control in children and adolescents with type 1 diabetes: a case-control study
  6. Determinants of childhood and adolescent obesity and it’s effect on metabolism in South Indian population
  7. Evaluation of continuous glucose monitoring and nutritional status in glycogen storage diseases
  8. Retrospective assessment of hepatic involvement in patients with inherited metabolic disorders: nine-year single-center experience
  9. Relationships among biological sex, body composition, and bone mineral density in young persons with and without diabetes
  10. The clinical characteristics of 10 cases and adult height of six cases of rare familial male-limited precocious puberty
  11. Optimal timing of repeat thyroid fine-needle aspiration biopsy
  12. Medium-chain acyl-CoA dehydrogenase deficiency in North Macedonia – ten years experience
  13. The effect of antenatal steroids on metabolic bone disease of prematurity
  14. Prader-Willi syndrome gene expression profiling of obese and non-obese patients reveals transcriptional changes in CLEC4D and ANXA3
  15. Early-onset growth hormone treatment in Prader–Willi syndrome attenuates transition to severe obesity
  16. Case Reports
  17. Neonatal severe hyperparathyroidism with inactivating calcium sensing receptor (CaSR) mutation (p.I81K)
  18. Clinical manifestations and molecular genetics of seven patients with Niemann–Pick type-C: a case series with a novel variant
  19. Expanding the genotypic spectrum of 3β-hydroxy-δ5-C27-steroid dehydrogenase (HSD3B7) deficiency: novel mutations and clinical outcomes
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