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An autosomal dominant hypophosphatemic rickets phenotype in a Tunisian family caused by a new FGF23 missense mutation

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Abstract

Autosomal dominant hypophosphatemic rickets (ADHR) is a rare disease, characterized by isolated renal phosphate wasting, hypophosphatemia, and inappropriately normal 1,25-dihydroxyvitamin D3 (calcitriol) levels. This syndrome involves rickets with bone deformities in childhood and osteomalacia, osteoporosis, articular and para-articular pain, and fatigue in adulthood. It is caused by mutations in a consensus sequence for proteolytic cleavage of the FGF23 protein. Normally, this protein actively regulates phosphate homeostasis. Here we report a Tunisian family in which one parent and three children show clinical and biological features of ADHR. Mutation analysis of the FGF23 gene finds a heterozygous substitution of the C at position 526 by a T (526 C → T), leading to an amino acid replacement of the FGF23 protein (R176W) at position 176. This causative new mutation is located in the consensus sequence for the proteolytic cleavage domain. These results confirm the importance of this site in FGF23 function and its essential role in ADHR physiopathology.

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Acknowledgments

We are indebted to Sihem Sassi, Ahlem Msakni, and Hedi Laatiri for their excellent technical help.

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Authors and Affiliations

  1. Laboratoire de Cytogénétique, de Génétique Moléculaire et de Biologie de la Reproduction Humaines, Hôpital Farhat Hached, Rue Ibn El Jazzar, 4000, Sousse, Tunisia

    Moez Gribaa, Yosra Bouyacoub, Ilhem Ben Charfeddine, Labiba Adala, Ons Mamay & Ali Saad

  2. Service de Rhumatologie, Hôpital Fattouma Bourguiba, 5000, Monastir, Tunisia

    Mohamed Younes, Wided Korbaa, Mongi Touzi & Naceur Bergaoui

Authors
  1. Moez Gribaa
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  2. Mohamed Younes
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  3. Yosra Bouyacoub
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  4. Wided Korbaa
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  5. Ilhem Ben Charfeddine
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  6. Mongi Touzi
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  7. Labiba Adala
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  8. Ons Mamay
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  9. Naceur Bergaoui
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  10. Ali Saad
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Correspondence to Moez Gribaa.

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Gribaa, M., Younes, M., Bouyacoub, Y. et al. An autosomal dominant hypophosphatemic rickets phenotype in a Tunisian family caused by a new FGF23 missense mutation. J Bone Miner Metab 28, 111–115 (2010). https://doi.org/10.1007/s00774-009-0111-5

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  • DOI: https://doi.org/10.1007/s00774-009-0111-5

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