Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC).
Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone.(1) In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys.
Departments of Oral Biology and Pediatric Dentistry, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of Human Genetics, Graduate School of Public Health; Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Alexandre R
AR
Vieira
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
Moses
M
Lee
Medical Genetics Service, Hospital de Clínicas de Porto Alegre, RS, Brazil.
Filippo
F
Vairo
Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, RS, Brazil.
Julio Cesar
JC
Loguercio Leite
Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, RS, Brazil.
Maria Cristina
MC
Munerato
Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, RS, Brazil.
Fernanda
F
Visioli
Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, RS, Brazil.
Stéphanie Rodrigues
SR
D'Ávila
Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.
Shih-Kai
SK
Wang
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea. Electronic address: Murimchoi@snu.ac.kr.
Murim
M
Choi
Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.
James P
JP
Simmer
Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.
Jan C-C
JC
Hu
D000293:Adolescent; D002114:Calcinosis / Q000150:complications* / Q000235:genetics*; D003805:Dentin Dysplasia / Q000209:etiology*; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D006958:Hyperostosis, Cortical, Congenital / Q000150:complications* / Q000235:genetics*; D054559:Hyperphosphatemia / Q000150:complications* / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011862:Radiography, Panoramic; D014092:Tooth Root / Q000002:abnormalities*; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D000089703:Fibroblast Growth Factor-23; D017350:N-Acetylgalactosaminyltransferases; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C000717427:FGF23 protein, human