Familial hypophosphatemic rickets caused by a PHEX gene mutation accompanied by a NPR2 missense mutation

Yongting Zhao; Fan Yang; Lihong Wang; Hui Che

doi:10.1515/jpem-2019-0380

Article

Familial hypophosphatemic rickets caused by a PHEX gene mutation accompanied by a NPR2 missense mutation

Yongting Zhao , Fan Yang , Lihong Wang and Hui Che

Published/Copyright: January 13, 2020

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 33 Issue 2

Abstract

Background

Familial hypophosphatemic rickets, which is usually acknowledged as X-linked hypophosphatemic rickets (XLH), is a rare hereditary disease. XLH caused by mutations in the PHEX gene often manifests as growth retardation, skeletal deformities, osteodynia and dental dysplasia. NPR2 mutations are reported to cause disproportionate short stature. Our study was designed to identify the gene mutations of three patients in one family.

Case description

A 40-year-old Chinese male visited the hospital for continuous osteodynia and presented with bilateral leg bowing, absent teeth and a progressive limp. The age of onset was approximately 2 years old. His 63-year-old mother and 42-year-old brother both shared identical symptoms with him. The laboratory tests were consistent with XLH, which showed decreased levels of blood phosphorus and 1,25-dihydroxyvitamin D₃ as well as increased urinary phosphorus excretion. Mutation analysis revealed that the proband as well as his mother and his brother all had a PHEX mutation in exon 14 (c.1543C > T), and the proband also had a NPR2 mutation in exon 21 (c.3058C > T).

Conclusions

We report the familial hypophosphatemic rickets of three patients in a Chinese family caused by a PHEX gene mutation in exon 14 (c.1543C > T), which had never been reported in Chinese patients. We first report an XLH case together with a NPR2 mutation that had never been reported before.

Keywords: NPR2; PHEX; X-linked hypophosphatemic rickets

Corresponding authors: Lihong Wang, PhD, Department of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, Harbin, P.R. China; and Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jpem-2019-0380).

Received: 2019-08-16

Accepted: 2019-11-29

Published Online: 2020-01-13

Published in Print: 2020-02-25

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Supplementary Material

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https://doi.org/10.1515/jpem-2019-0380

Keywords for this article

NPR2; PHEX; X-linked hypophosphatemic rickets