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A Novel Synonymous Variant of PHEX in a Patient with X-Linked Hypophosphatemia

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Abstract

X-linked dominant hypophosphatemia (XLH), the most common form of hereditary hypophosphatemic rickets/osteomalacia, is caused by loss-of-function phosphate-regulating endopeptidase homolog X-linked gene (PHEX) variants. However, synonymous PHEX variants are rare in XLH. We report a 7-year-old boy with hypophosphatemia, short stature, and lower limb deformity. Whole-exome sequencing, reverse transcription–polymerase chain reaction, and Sanger sequencing were performed to identify the pathogenicity of the variant. A novel synonymous PHEX variant (NM_000444.4:c.1530 C>T, p.Arg510Arg) was detected in the proband. Further analysis revealed a 58-bp deletion at the 5′ site of exon 14 during splicing. This study extends the genetic spectrum of XLH and confirms the rarity and significance of synonymous PHEX variants.

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Funding

This work was supported by CAMS Innovation Fund for Medical Sciences (Grant Nos. 2021-I2M-1-002 and 2020-I2M-C&T-B-016), the National Key R&D Program of China (Grant No. 2021YFC2501700), and the National Natural Science Foundation of China (Grant No. 81970757).

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Authors and Affiliations

  1. Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China

    Xiaosen Ma, Qianqian Pang, Yan Jiang, Ou Wang, Mei Li, Xiaoping Xing & Weibo Xia

  2. Laboratory Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China

    Qi Zhang

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  1. Xiaosen Ma
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Contributions

WX and XM designed the study and prepared the first draft of the paper. WX is guarantor. XM, QP, and QZ contributed to the experimental work. WX, YJ, OW, ML, and XX revised the paper critically for intellectual content. All authors approved the final version. XM and WX agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.

Corresponding author

Correspondence to Weibo Xia.

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Conflict of interest

Xiaosen Ma, Qianqian Pang, Qi Zhang, Yan Jiang, Ou Wang, Mei Li, Xiaoping Xing, and Weibo Xia declare no conflict of interest.

Human and Animal Rights

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of PUMCH (JS-1689).

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Written informed consent was obtained from the parents.

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Ma, X., Pang, Q., Zhang, Q. et al. A Novel Synonymous Variant of PHEX in a Patient with X-Linked Hypophosphatemia. Calcif Tissue Int 111, 634–640 (2022). https://doi.org/10.1007/s00223-022-01003-w

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