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A novel missense mutation in GALNT3 causing hyperostosis-hyperphosphataemia syndrome
Hannes Olauson1, Tijana Krajisnik, Charlotta Larsson
1Department of Medical Sciences, Uppsala University Hospital, Ing.70, 3 tr, 75185 Uppsala, Sweden.
European Journal of Endocrinology
|March 7, 2008
Summary
A novel mutation in GALNT3 causes Hyperostosis-hyperphosphataemia syndrome (HHS). This genetic defect leads to altered FGF23 processing, resulting in hyperphosphataemia and bone abnormalities.
Area of Science:
- Genetics
- Biochemistry
- Endocrinology
Background:
- Hyperostosis-hyperphosphataemia syndrome (HHS) is a rare genetic disorder.
- It is characterized by high phosphate levels, normal/high vitamin D, and painful bone overgrowth.
- Inactivating mutations in GALNT3 gene cause HHS.
Observation:
- A 19-year-old Colombian girl presented with hyperphosphataemia and tibial hyperostosis.
- Genetic analysis revealed a new homozygous missense mutation (R438H) in the GALNT3 gene.
- This mutation was not found in controls or public databases.
Findings:
- The R438H mutation is predicted to disrupt GALNT3 protein structure and function.
- Serum levels showed decreased intact FGF23 and increased C-terminal FGF23.
- This indicates differential processing of the phosphaturic factor FGF23.
Implications:
- This is the first reported missense mutation in GALNT3 causing HHS.
- The R438H substitution likely impairs GALNT3 activity, leading to increased FGF23 degradation.
- This mechanism explains the observed hyperostosis and hyperphosphataemia in HHS.
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