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Novel variants and uncommon cases among southern Chinese children with X-linked hypophosphatemia



X-linked hypophosphatemia (XLH) is the most common inherited renal phosphate wasting disorder and is often misdiagnosed as vitamin D deficiency. This study aims to provide clinical and mutational characteristics of 65 XLH pediatric patients in southern China.


In this work, a combination of DNA sequencing and qPCR analysis was used to study the PHEX gene in 80 pediatric patients diagnosed with hypophosphatemia. The clinical and laboratory data of confirmed 65 XLH patients were assessed and analyzed retrospectively.


In 65 XLH patients from 61 families, 51 different variants in the PHEX gene were identified, including 23 previously reported variants and 28 novel variants. In this cohort of XLH patients, the c.1601C>T(p.Pro534Leu) variant appears more frequently. Fourteen uncommon XLH cases were described, including four boys with de novo mosaic variants, eight patients with large deletions and a pair of monozygotic twins. The clinical manifestations in this cohort are very similar to those previously reported.


This study extends the mutational spectrum of the PHEX gene, which will contribute to accurate diagnosis. This study also suggests a supplementary qPCR or MLPA assay may be performed along with classical sequencing to confirm the gross insertion/deletion.

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We would like to thank the enrolled family for participation in this study. We thank Dr. Gendie Lash at Guangzhou Women and Children's Medical Center and Dr. Ting Wu for correcting the English of our manuscript. We also thank the Department of Radiology and Clinical Laboratory at Guangzhou Women and Children’s Medical Center for assistance with radiological and laboratory examinations.


This work was supported in part by the National Natural Science Foundation of China (Grant number 81701128), and the fund from Guangzhou Institute of Pediatrics/Guangzhou Women and Children’s Medical Center (Grant number Pre-NSFC-2019-008).

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Authors and Affiliations



All the listed authors were involved in drafting or editing this article, and approved its submission and publication. LL and CZ conceived and designed the study. LL, CZ, XL, JC, YH, XM, ZZ, WZ, CL, ZL, JX and YL recruited the family, collected their medical history and data, and inquired the family pedigree. YL, JX, HS, LS, MW, YC, DW, ZL and XY performed the experiments and acquired the data. YL and JX analyzed the data. LL, CZ and YL wrote the paper.

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Correspondence to C. Zeng or L. Liu.

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The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Institutional Review Board of Guangzhou Women and Children’s Medical Center (Guangzhou, China) (No. 2015-82).

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Informed consent was obtained from all the subjects or their tutors (for under-aged participants).

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Lin, Y., Xu, J., Li, X. et al. Novel variants and uncommon cases among southern Chinese children with X-linked hypophosphatemia. J Endocrinol Invest 43, 1577–1590 (2020).

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  • X-linked hypophosphatemia
  • PHEX gene
  • Southern China
  • Mutational spectrum
  • Clinical features