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

Calcif Tissue Int. 2022 Dec;111(6):634-640. doi: 10.1007/s00223-022-01003-w.

PMID: 35831717

Xiaosen Ma, Qianqian Pang, Qi Zhang

Highlights: This study extends the genetic spectrum of XLH and confirms the rarity and significance of synonymous PHEX variants.

Abstract

Background: The most prevalent type of hereditary hypophosphatemic rickets/osteomalacia, X-linked dominant hypophosphatemia (XLH), is brought on by loss-of-function variants in the PHEX gene, which encodes phosphate-regulating endopeptidase. Conversely, homologous PHEX mutations in XLH are uncommon.

Results: This case study involves a young child aged 7 who has hypophosphatemia, short stature, and lower limb deformity. To determine the pathogenicity of the variant, whole-exome sequencing, reverse transcription-polymerase chain reaction, and Sanger sequencing were carried out. The proband had a novel synonymous PHEX variant (NM 000444.4:c.1530 C>T, p.Arg510Arg). A 58-bp loss during splicing was found at the 5' location of exon 14 after further research.

Conclusion: The genetic range of XLH is expanded by this study, which also supports the relevance and rarity of synonymous PHEX variations.

Keywords: PHEX, Splice site, Synonymous variant, XLH