X-linked hypophosphatemia in 4 generations due to an exon 13-15 duplication in PHEX, in the absence of the c.*231A>G variant

Bone. 2023 Jul;172:116763. doi: 10.1016/j.bone.2023.116763.

PMID: 37059315

Julio Soto Barros, Sabrina I Sanchez, Kristin Cabral

Highlights: This article presents a family with X-linked hypophosphatemia (XLH) who harbors the exon 13-15 duplication but does not carry the 3'UTR variant.

Abstract

Background: Due to inactivating PHEX variants, X-linked hypophosphatemia (XLH) is the most prevalent cause of inherited rickets. More than 800 variants have been identified so far, and one, with a single base change c.*231A>G in the 3' untranslated region (UTR), has been reported to be common in North America. It is uncertain if the pathogenicity is due only to the c.*231A>G mutation because an exon 13–15 duplication has just been discovered to occur in conjunction with the variant.

Conclusion: As proof that the duplication itself is the pathogenic variant when these two variants are detected in cis, this study describes a family with XLH that carries the exon 13–15 duplication but not the 3’UTR variant.

Keywords: Phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX), Rickets, X-linked hypophosphatemia (XLH)