Thus, this report describes the first case, to our knowledge, of autoimmune hyperphosphatemic tumoral calcinosis with pathogenic autoantibodies targeting FGF23.
Further phenotype studies undertaken in Ecalc1 (kl203X/203X) mice demonstrated elevations in plasma concentrations of phosphate, FGF23 and 1,25-dihydroxyvitamin D. Thus, two allelic variants of Kl that develop EC and represent mouse models for tumoural calcinosis have been established.
Severe vascular calcification and tumoral calcinosis in a family with hyperphosphatemia: a fibroblast growth factor 23 mutation identified by exome sequencing.
Impaired O-glycosylation of FGF23 due to the lack of UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyl-transferase 3 (GALNT3) or due to certain homozygous FGF23 mutations results in reduced secretion of intact FGF23 and leads to familial hyperphosphatemic tumoral calcinosis.
Defective O-glycosylation due to a novel homozygous S129P mutation is associated with lack of fibroblast growth factor 23 secretion and tumoral calcinosis.
In summary, we have detected novel GALNT3 mutations that result in familial TC, and show that disturbed serum FGF23 concentrations are present in our TC cases as well as in previously reported cases.
Familial tumoral calcinosis is characterized by ectopic calcifications and hyperphosphatemia due to inactivating mutations in FGF23 or UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3).
Recent investigations indicate that excess actions of FGF23 cause several hypophosphatemic diseases whereas deficient FGF23 activity results in hyperphosphatemic tumoral calcinosis.
Familial tumoral calcinosis (TC), characterized by ectopic calcifications and hyperphosphatemia, is caused by mutations in the GALNT3 or fibroblast growth factor 23 (FGF23) genes.
One form of TC is caused by homozygous inactivating GALNT3 mutations implying that the encoded enzyme, which is involved in the initiation of O-glycosylation, is important for preventing cleavage of FGF-23 into biologically inactive fragments.
Serum matrix extracellular phosphoglycoprotein levels, however, were normal in the family with GALNT3-TC and a kindred with TC carrying the FGF23S71G mutation.
The objective was to identify mutations in FGF23 or GALNT3 responsible for a mild TC phenotype by DNA sequencing and to determine serum FGF23 levels by ELISA.
Our understanding of FGF23 will help to develop novel therapies for phosphate wasting disorders, as well as for disorders of increased serum phosphate, such as tumoral calcinosis, a rare disorder, and renal failure, a common disorder.
Impaired O-glycosylation of FGF23 due to the lack of UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyl-transferase 3 (GALNT3) or due to certain homozygous FGF23 mutations results in reduced secretion of intact FGF23 and leads to familial hyperphosphatemic tumoral calcinosis.
A case of familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome due to a compound heterozygous mutation in GALNT3 demonstrating new phenotypic features.
Recessive mutations in the mucin-like glycosyltransferase GalNAc transferase-3 (GALNT3) and the phosphaturic hormone fibroblast growth factor-23 (FGF23) have been shown to result in TC.
The objective was to identify mutations in FGF23 or GALNT3 responsible for a mild TC phenotype by DNA sequencing and to determine serum FGF23 levels by ELISA.