title: Human Preosteoblastic Cell Culture from a Patient with Severe Tumoral Calcinosis-Hyperphosphatemia Due to a New GALNT3 Gene Mutation: Study of In Vitro Mineralization.
abstract: Human disorders of phosphate (Pi) handling and skeletal mineralization represent a group of rare bone diseases. One of these disease is tumoral calcinosis (TC). In this study, we present the case of a patient with TC with a new GALNT3 gene mutation. We also performed functional studies using an in vitro cellular model. Genomic DNA was extracted from peripheral blood collected from a teenage Caucasian girl affected by TC, and from her parents. A higher capability to form mineralization nodules in vitro was found in human preosteoblastic cells of mutant when compared to wild-type controls. We found a novel homozygous inactivating splice site mutation in intron I (c.516-2a>g). A higher capability to form mineralization nodules in vitro was found in the mutant cells in human preosteoblastic cells when compared to wild-type controls. Understanding the functional significance and molecular physiology of this novel mutation will help to define the role of FGF23 in the control of Pi homeostasis in normal and in pathological conditions.
authors.affiliation: Metabolic Bone Diseases Unit AOUC-Careggi, Department of Orthopedics, University of Florence, Largo Palagi, 1, 50134, Florence, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Masi
authors.forename: G
authors.initials: G
authors.lastname: Beltrami
authors.forename: S
authors.initials: S
authors.lastname: Ottanelli
authors.forename: F
authors.initials: F
authors.lastname: Franceschelli
authors.forename: A
authors.initials: A
authors.lastname: Gozzini
authors.forename: R
authors.initials: R
authors.lastname: Zonefrati
authors.forename: G
authors.initials: G
authors.lastname: Galli
authors.forename: S
authors.initials: S
authors.lastname: Ciuffi
authors.forename: C
authors.initials: C
authors.lastname: Mavilia
authors.forename: F
authors.initials: F
authors.lastname: Giusti
authors.forename: G
authors.initials: G
authors.lastname: Marcucci
authors.forename: F
authors.initials: F
authors.lastname: Cioppi
authors.forename: E
authors.initials: E
authors.lastname: Colli
authors.forename: C
authors.initials: C
authors.lastname: Fossi
authors.forename: A
authors.initials: A
authors.lastname: Franchi
authors.forename: C
authors.initials: C
authors.lastname: Casentini
authors.forename: R
authors.initials: R
authors.lastname: Capanna
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Brandi
mesh_terms: D001483:Base Sequence; D002114:Calcinosis / Q000235:genetics*; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002648:Child; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005434:Flow Cytometry; D006801:Humans; D006958:Hyperostosis, Cortical, Congenital / Q000235:genetics*; D054559:Hyperphosphatemia / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics*; D010006:Osteoblasts / Q000473:pathology*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013234:Stem Cells / Q000473:pathology; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D000089703:Fibroblast Growth Factor-23; D017350:N-Acetylgalactosaminyltransferases; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C000717427:FGF23 protein, human