PHEX analysis in 118 pedigrees reveals new genetic clues in hypophosphatemic rickets
- 15 February 2009
- journal article
- Published by Springer Science and Business Media LLC in Human Genetics
- Vol. 125 (4), 401-411
- https://doi.org/10.1007/s00439-009-0631-z
Abstract
Familial hypophosphatemic rickets is a rare disease, which is mostly transmitted as an X-linked dominant trait, and mutations on the phosphate regulating gene with homologies to endopeptidases on the X-chromosome (PHEX) gene are responsible for the disease in most familial cases. In this study we analyzed PHEX in a large cohort of 118 pedigrees representing 56 familial cases and 62 sporadic cases. The high-resolution melting curves technique was tested as a screening method, along with classical sequencing. PHEX mutations have been found in 87% of familial cases but also in 72% of sporadic cases. Missense mutations were found in 16 probands, two of which being associated with other PHEX mutations resulting into truncated proteins. By plotting missense mutations described so far on a 3D model of PHEX we observed that these mutations focus on two regions located in the inner part of the PHEX protein. Family members of 13 sporadic cases were analyzed and a PHEX mutation was detected in one of the apparently healthy mother. These results highlight the major role of PHEX in X-linked dominant hypophosphatemic rickets, and give new clues regarding the genetic analysis of the disease. A screening of the different family members should be mandatory when a PHEX mutation is assessed in a sporadic case and the search for another PHEX mutation should be systematically proceed when facing a missense mutation.This publication has 34 references indexed in Scilit:
- Hereditary Hypophosphatemic Rickets with Hypercalciuria Is Caused by Mutations in the Sodium-Phosphate Cotransporter Gene SLC34A3American Journal of Human Genetics, 2006
- Information for the Coordinates of Exons (ICE): a human splice sites databaseGenomics, 2004
- The Wrickkened Pathways of FGF23, MEPE and PHEXCritical Reviews in Oral Biology & Medicine, 2004
- Disease-causing missense mutations in the PHEX gene interfere with membrane targeting of the recombinant proteinHuman Molecular Genetics, 2001
- Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23Nature Genetics, 2000
- Three Novel PHEX Gene Mutations in Japanese Patients with X-Linked Hypophosphatemic RicketsPediatric Research, 2000
- Developmental Expression and Tissue Distribution of Phex Protein: Effect of the Hyp Mutation and Relationship to Bone MarkersJournal of Bone and Mineral Research, 2000
- Genomic Organization of the Human PEX Gene Mutated in X-Linked Dominant Hypophosphatemic RicketsGenome Research, 1997
- Mutational analysis of the PEX gene in patients with X-linked hypophosphatemic rickets.1997
- A common molecular basis for three inherited kidney stone diseasesNature, 1996