<Emphasis Type="Italic">PHEX</Emphasis> analysis in 118 pedigrees reveals new genetic clues in hypophosphatemic rickets |
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Authors: | Céline Gaucher Odile Walrant-Debray Thy-Minh Nguyen Laure Esterle Michèle Garabédian Frédéric Jehan |
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Institution: | 1.Inserm U561, H?pital Saint-Vincent-de-Paul,Paris,France;2.EA2496, Dental School, Université Paris-Descartes,Paris,France |
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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.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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