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

Abstract

X-linked hypophosphatemia is the most common cause of inherited rickets, due to inactivating variants of PHEX. More than 800 variants have been described to date and one which consists of a single base change in the 3' untranslated region (UTR) (c.*231A>G) is reported as prevalent in North America. Recently an exon 13-15 duplication has been found to occur in concert with the c.*231A>G variant, and thus it is unclear whether the pathogenicity is solely a function of the UTR variant. We present a family with XLH who harbors the exon 13-15 duplication but does not carry the 3'UTR variant, providing evidence that the duplication itself is the pathogenic variant when these two variants are found in cis.