Two novel variants of the PHEX gene in patients with X‑linked dominant hypophosphatemic rickets and prenatal diagnosis for fetuses in these families

Liao,Hong; Zhu,Hong‑Mei; Liu,Hong‑Qian; Li,Ling‑Ping; Liu,Shan‑Ling; Wang,He

doi:10.3892/ijmm.2018.3402

Two novel variants of the PHEX gene in patients with X‑linked dominant hypophosphatemic rickets and prenatal diagnosis for fetuses in these families

Authors:
- Hong Liao
- Hong‑Mei Zhu
- Hong‑Qian Liu
- Ling‑Ping Li
- Shan‑Ling Liu
- He Wang
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Affiliations: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: January 18, 2018 https://doi.org/10.3892/ijmm.2018.3402
Pages: 2012-2020
Copyright: © Liao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

X‑linked hypophosphatemic rickets (XLHR; OMIM 307800) is an X‑linked dominant disorder caused by mutations in the phosphate‑regulating neutral endopeptidase homolog X‑linked (PHEX) gene, which is located at Xp22.11. In the present study, two novel variants of the PHEX gene were identified in two unrelated families with XLHR by directly sequencing all 22 exon regions and intron/exon boundaries of the PHEX gene. One missense variant, NM_000444.5: c.1721T>A, was identified in exon 17 of the PHEX gene in Family 1, which led to an amino acid change in the p.Ile574Lys protein. The other splicing variant identified was NM_000444.5: c.591A>G, in exon 5 in Family 2, resulting in a deletion of 77 bp in the 3' site of exon 5 during splicing, which was verified by direct cDNA sequencing of the PHEX gene. According to the results of reverse transcription‑quantitative polymerase chain reaction analysis, the affected male with the splicing variant c.591A>G showed normal gene expression of PHEX, whereas the affected female exhibited low gene expression, compared with normal females. Based on these findings, prenatal diagnoses were made for the fetuses with a family history of XLHR using the backup amniotic fluid samples. One fetus without the missense variant was confirmed to be a healthy girl in a follow‑up visit 1 month following birth.

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