title: Periodontal disease and FAM20A mutations.
abstract: Enamel-renal-gingival syndrome (ERGS; OMIM #204690), a rare autosomal recessive disorder caused by mutations in FAM20A, is characterized by nephrocalcinosis, nephrolithiasis, amelogenesis imperfecta, hypoplastic type, gingival fibromatosis and other dental abnormalities, including hypodontia and unerupted teeth with large dental follicles. We report three patients and their families with findings suggestive of ERGS. Mutation analysis of FAM20A was performed in all patients and their family members. Patients with homozygous frameshift and compound heterozygous mutations in FAM20A had typical clinical findings along with periodontitis. The other had a novel homozygous missense mutation in exon 10, mild gingival fibromatosis and renal calcifications. The periodontitis in our patients may be a syndrome component, and similar findings in previous reports suggest more than coincidence. Fam20a is an allosteric activator that increases Fam20c kinase activity. It is hypothesized that lack of FAM20A activation of FAM20C in our patients with FAM20A mutations might have caused amelogenesis imperfecta, abnormal bone remodeling and periodontitis. Nephrocalcinosis appears not to be a consistent finding of the syndrome and the missense mutation may correlate with mild gingival fibromatosis. Here we report three patients with homozygous or compound heterozygous mutations in FAM20A and findings that extend the phenotypic spectrum of this disorder, showing that protein truncation is associated with greater clinical severity.
authors.affiliation: Center of Excellence in Medical Genetics Research, Chiang Mai University, Chiang Mai, Thailand.|Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.|Dentaland Clinic, Chiang Mai, Thailand.
authors.forename: Piranit Nik
authors.initials: PN
authors.lastname: Kantaputra
authors.affiliation: Center of Excellence in Medical Genetics Research, Chiang Mai University, Chiang Mai, Thailand.|Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Chotika
authors.initials: C
authors.lastname: Bongkochwilawan
authors.affiliation: No Affiliation, Wauwatosa, WI, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Lubinsky
authors.affiliation: Faculty of Associated Medical Sciences, Division of Clinical Immunology, Department of Medical Technology, Chiang Mai University, Chiang Mai, Thailand.|Biomedical Technology Research Center, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at the Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Supansa
authors.initials: S
authors.lastname: Pata
authors.affiliation: Center of Excellence in Medical Genetics Research, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Massupa
authors.initials: M
authors.lastname: Kaewgahya
authors.affiliation: Discipline of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, National University of Singapore, Singapore, Singapore.
authors.forename: Huei Jinn
authors.initials: HJ
authors.lastname: Tong
authors.affiliation: School of Biochemistry, Institute of Science, and Center for Biomolecular Structure, Function and Application, Suranaree University of Technology, Nakhon Ratchasima, Thailand.|Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand.
authors.forename: James R
authors.initials: JR
authors.lastname: Ketudat Cairns
authors.affiliation: Faculty of Dentistry, Department of Pedodontics, Istanbul University, Istanbul, Turkey.
authors.forename: Yeliz
authors.initials: Y
authors.lastname: Guven
authors.affiliation: Dental Department, Lampang Hospital, Lampang, Thailand.
authors.forename: Nipon
authors.initials: N
authors.lastname: Chaisrisookumporn
mesh_terms: D002648:Child; D002675:Child, Preschool; D003746:Dental Enamel Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010510:Periodontal Diseases / Q000000981:diagnostic imaging / Q000235:genetics*
chemical_list: D003746:Dental Enamel Proteins; C571509:FAM20A protein, human