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Pekkarinen, T.A.* ; Lorenz-Depiereux, B. ; Lohman, M.* ; Mäkitie, O.M.*

Unusually severe hypophosphatemic rickets caused by a novel and complex re-arrangement of the PHEX gene.

Am. J. Med. Genet. A 164, 2931-2937 (2014)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
X-linked hypophosphatemia (XLH) is caused by mutations in PHEX. Several other genetic forms of hypophosphatemia have also been described. These disorders share variable clinical presentation ranging from mild hypophosphatemia to severe lower extremity bowing. We report on a 43-year-old woman with short stature, painful leg deformities, and poor dentation. Her biochemical profile showed hypophosphatemia with renal phosphate wasting. Due to unusually severe clinical presentation and absence of mutations in Sanger sequencing of the PHEX gene, quantitative multiplex ligation-dependent probe amplification was performed. A large deletion within the PHEX gene encompassing exons 8 to 11 was identified. We generated a specific junction fragment using long-range PCR and sequenced the junction fragment to determine the exact deletion breakpoints. We found a heterozygous novel complex re-arrangement involving gross deletions, insertions, and inversion of PHEX (hg19:g.22,115,003_22,141,395del;g:22,145,536_22,150,789delinsCins22,114,640_22,114,698invinsA). Thus, the complex re-arrangement including a deletion of coding exons 8 to 11 of the PHEX can be regarded as the cause of XLH in the patient reported here. Phosphate and active vitamin D treatment was initiated with subsequent relief in bone pain and physical improvement. This report expands the spectrum of clinical severity underlying genetic defects in XLH and highlights the importance of conventional medical therapy even at adult age. Furthermore, our findings underscore the importance of search for gene deletions in patients with suspected XLH.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Novel Deletions/insertion In Phex Gene ; Severe Phenotype ; X-linked Hypophosphatemia; X-linked Hypophosphatemia; Mutational Analysis; Dmp1; Fgf23; Adults; Diagnosis; Phosphate; Density; Cohort
ISSN (print) / ISBN 0148-7299
e-ISSN 1096-8628
Journal American Journal of Medical Genetics, Part A
Quellenangaben Volume: 164, Issue: 11, Pages: 2931-2937 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)