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Genotype and Phenotype of Renal Hypouricemia: A Single-Center Study from China

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Abstract

Background

Renal hypouricemia (RHUC), a rare inherited disorder characterized by impaired uric acid reabsorption and subsequent profound hypouricemia, occurs mainly due to variants in SLC22A12 or SLC2A9. Only anecdotal cases and one small-scale RHUC screening study have been reported in the Chinese population.

Methods

A total of 19 patients with RHUC from 17 unrelated families were recruited from our center. The medical history, clinical manifestations, biochemical exam, and clinical outcomes were collected. Next-generation sequencing-based targeted gene sequencing or whole exon sequencing was performed.

Results

A total of 22 variants in SLC22A12 or SLC2A9 were found in 19 patients. The variant c.944G>A (p.W315X) in SLC2A9 was identified in three patients. Three variants c.165C>A (p.D55E), c.1549_1555delGAGACCC (p.E517Rfs*17), and c.1483T>C (p.W495R) in SLC22A12 and three variants c.1215+1G>A (splicing variant), c.643A>C (p.T215P), and c.227C>A (p.S76X) in SLC2A9 were novel. A proportion of 10 out of 19 patients presented with exercise-induced acute kidney injury (EIAKI). The renal outcome was favorable. Five patients had nephrolithiasis, in whom three had hypercalciuria.

Conclusion

The current study reported six novel variants in SLC22A12 and SLC2A9 genes of Chinese patients with RHUC. The variant c.944G>A (p.W315X) in SLC2A9 may be common in Chinese patients. EIAKI is the main clinical phenotype associated with RHUC in our cohort, with a favorable outcome. Hypercalciuria presented in some RHUC patients is a new finding.

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Acknowledgement

Special thanks are given to Dr. Yong Du for his guidance with writing the manuscript.

Author information

Authors and Affiliations

  1. Department of Nephrology, Zhejiang University School of Medicine Second Affiliated Hospital, Jiefang Rd 88, Hangzhou, 310009, Zhejiang, China

    Lijun Mou, Lina Zhu & Ying Hu

  2. Division of Nephrology, Huashan Hospital Fudan University, Shanghai, China

    Xujiao Chen

  3. Department of Nephrology, Zhejiang University School of Medicine Second Affiliated Hospital Jiande Branch, Jiande, Zhejiang, China

    Hong Zhu

  4. Kidney Disease Center, Institute of Nephrology, Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang University, School of Medicine First Affiliated Hospital, Hangzhou, Zhejiang, China

    Ying Xu

Authors
  1. Lijun Mou
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  2. Lina Zhu
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  4. Ying Hu
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Corresponding author

Correspondence to Lina Zhu.

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Funding

This study was supported by Zhejiang Provincial Natural Science Foundation of China [LY23H050002].

Conflicts of Interest

The authors (Lijun Mou, Lina Zhu, Xujiao Chen, Ying Hu, Hong Zhu, Ying Xu) report that there are no competing interests to declare.

Availability Of Data And Material

The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive (Genomics, Proteomics and Bioinformatics 2021) in the National Genomics Data Center (Nucleic Acids Res 2021), and China National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences (GSA: HRA004533) that are publicly accessible at https://ngdc.cncb.ac.cn/gsa. [40, 41]. The data will be shared on reasonable request to the corresponding author.

Ethical Approval of Studies

Study approval statement: This study protocol was reviewed and approved by the Ethics Committee of Zhejiang University School of Medicine Second Affiliated Hospital. The approval number was 2021-0427. Consent to participate statement: Written informed consents were obtained from all participants to participate in the study.

Consent to Participate

Informed consents were obtained from all subjects involved in the study.

Consent for Publication

Not applicable.

Code Availability

Not applicable.

Author Contributions

Lijun Mou and Lina Zhu conceived the idea, and designed and planned the study; Xujiao Chen, Ying Hu, Hong Zhu, and Ying Xu gave important suggestions on study design and improved the study protocol; all authors participated in the collection of samples and the clinical data of patients; Ying Hu and Ying Xu analyzed the data; Lijun Mou and Lina Zhu drafted the manuscript and designed the figures; all authors discussed and interpreted the results, commented on the manuscript, provided critical feedback, and helped shape the research; and all authors read and approved the final manuscript.

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Mou, L., Zhu, L., Chen, X. et al. Genotype and Phenotype of Renal Hypouricemia: A Single-Center Study from China. Mol Diagn Ther 28, 87–99 (2024). https://doi.org/10.1007/s40291-023-00683-w

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