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- Title
PHEX analysis in 118 pedigrees reveals new genetic clues in hypophosphatemic rickets.
- Authors
Gaucher, Céline; Walrant-Debray, Odile; Nguyen, Thy-Minh; Esterle, Laure; Garabédian, Michèle; Jehan, Frédéric
- 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.
- Subjects
RICKETS; BONE diseases; RARE diseases; X chromosome; GENETIC mutation; GENES
- Publication
Human Genetics, 2009, Vol 125, Issue 4, p401
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s00439-009-0631-z