Abstract
Absorptive hypercalciuria (AH) is a prevalent cause of kidney stones, and the adenylate cyclase 10 (ADCY10) gene is a rare causative gene of AH. This study aims to investigate the genotypic and phenotypic characteristics of patients with AH caused by ADCY10 gene mutations. Whole-exome sequencing and Sanger sequencing were performed on the probands and their family members, respectively. Clinical and genetic data of patients with AH caused by ADCY10 gene mutations were collected and analysed retrospectively from the present study and published literature. Two female patients (6 years old and 1 year old) with multiple bilateral kidney stones were found to have a heterozygous c.3304T>C mutation and a heterozygous c.1726C>T mutation in the ADCY10 gene. Urinary metabolite analysis revealed that urine calcium / creatinine ratios were 0.95 mmol/mmol and 1.61 mmol/mmol, respectively. Both patients underwent thiazide intake postoperatively, and upon reexamination, urine calcium decreased to within the normal range. A total of 61 patients with AH were reported from previous and present studies. The sex ratio was 7:5 for males to females, and the mean age of onset was 23.61±20.08 years. A total of 16 ADCY10 gene mutations were identified, including seven missense (43.75%), five splicing (31.25%), two frameshift (12.50%) and two nonsense mutations (12.50%). Only two cases were identified as homozygous mutations (c.1205_1206del), and the others were heterozygous mutations. In summary, we identified two novel ADCY10 gene candidate pathogenic variants in Chinese pediatric patients, which expands the mutational spectrum of the ADCY10 gene and provides a potential diagnostic and therapeutic target.
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We are grateful to the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding (XMLX202101) for the support to this work.
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All authors contributed to the study conception and design. Study design and data collection: Yucheng Ge and Wenying Wang. Yucheng Ge wrote the manuscript. Wenying Wang and Ye Tian revised the manuscript. Yucheng Ge, Ruichao Zhan, Yukun Liu and Zhenqiang Zhao prepared the figures and tables. All authors reviewed the manuscript. All authors contributed to revision and drafting of the article.
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Ge, Y., Liu, Y., Zhan, R. et al. Two novel heterozygous ADCY10 variants identified in Chinese pediatric patients with absorptive hypercalciuria: case report and literature review. J Genet 103, 5 (2024). https://doi.org/10.1007/s12041-023-01458-2
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DOI: https://doi.org/10.1007/s12041-023-01458-2