Abstract
Background
The aim of this study was to describe the genotypic and phenotypic characteristics of Chinese pediatric patients with hereditary nephrolithiasis.
Methods
Whole-exome sequencing (WES) was performed on 218 Chinese pediatric patients with kidney stones, and genetic and clinical data were collected and analyzed retrospectively.
Results
The median age at onset in our cohort was 2.5 years (age range, 0.3–13 years). We detected 79 causative mutations in 15 genes, leading to a molecular diagnosis in 38.99% (85/218) of all cases. Monogenic mutations were present in 80 cases, and digenic mutations were present in 5 cases; 34.18% (27/79) of mutations were not included in the databases. Six common mutant genes, i.e., HOGA1, AGXT, GRHPR, SLC3A1, SLC7A9, and SLC4A1, were found in 84.71% of the patients overall. Furthermore, three mutations (A278A, c.834_834 + 1GG > TT, and C257G) in HOGA1, two mutations (K12QfX156 and S275RfX28) in AGXT, and one mutation (C289DfX22) in GRHPR represented hotspot mutations. The patients with HOGA1 mutations had the earliest onset age (0.8 years), followed by those with SLC7A9 (1.8 years), SLC4A1 (2.7 years), AGXT (4.3 years), SLC3A1 (4.8 years), and GRHPR (8 years) mutations (p = 0.002). Nephrocalcinosis was most commonly observed in patients with AGXT gene mutations.
Conclusions
Fifteen causative genes were detected in 85 Chinese pediatric patients with kidney stone diseases. The most common mutant genes, novel mutations, hotspot mutations, and genotype–phenotype correlations were also found. This study contributes to the understanding of genetic profiles and clinical courses in pediatric patients with hereditary nephrolithiasis.
Graphical abstract
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Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
We are very grateful to the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding (XMLX202101) for supporting this work.
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All authors contributed to the study’s conception and design. Study design and data collection: Yukun Liu, Yucheng Ge, and Wenying Wang. Data statistical analysis/interpretation: Ruichao Zhan and Zhenqiang Zhao. Yucheng Ge and Yukun Liu wrote the manuscript. Wenying Wang and Jun Li revised the manuscript. Ruichao Zhan and Zhenqiang Zhao prepared Figures and Tables. All authors reviewed the manuscript. All authors contributed to the revision and drafting of the article.
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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Beijing Friendship Hospital, Capital Medical University (Date 02/01/2021/No. 2021-P2-019).
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Liu, Y., Ge, Y., Zhan, R. et al. Identification of mutations in 15 nephrolithiasis-related genes leading to a molecular diagnosis in 85 Chinese pediatric patients. Pediatr Nephrol 38, 3645–3661 (2023). https://doi.org/10.1007/s00467-023-06028-3
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DOI: https://doi.org/10.1007/s00467-023-06028-3