title: A novel AMELX mutation causes hypoplastic amelogenesis imperfecta.
abstract: OBJECTIVE
  Amelogenesis imperfecta (AI) is a hereditary genetic defect affecting tooth enamel. AI is heterogeneous in clinical phenotype as well as in genetic etiology. To date, more than 10 genes have been associated with the etiology of AI. Amelogenin is the most abundant enamel matrix protein, most of which is encoded by the amelogenin gene in the X-chromosome (AMELX). More than 16 alternative splicing transcripts have been identified in the murine Amelx gene. The purpose of this study was to identify the genetic cause of an AI family.
  
  
  METHODS
  We recruited a family with hypoplastic AI and performed mutational analysis on the candidate gene based on the clinical phenotype.
  
  
  RESULTS
  Mutational analysis revealed a missense mutation in exon 6 (NM_182680.1; c.242C > T), which changes a sequence in a highly conserved amino acid (NP_872621.1; p.Pro81Leu). Furthermore, a splicing assay using a minigene displayed that the mutation changed the mRNA splicing repertory.
  
  
  CONCLUSIONS
  In this study, we identified a novel AMELX missense mutation causing hypoplastic AI, and this mutation also resulted in altered mRNA splicing. These results will not only expand the mutation spectrum causing AI but also broaden our understanding of the biological mechanism of enamel formation.
authors.affiliation: Department of Pediatric Dentistry & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea. Electronic address: neokarma@snu.ac.kr.
authors.forename: Young-Jae
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Molecular Genetics & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea. Electronic address: dbswjdye@gmail.com.
authors.forename: Youn Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Pediatric Dentistry & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea. Electronic address: jennyk0824@naver.com.
authors.forename: Jenny
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Pediatric Dentistry & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea. Electronic address: snmc94@snu.ac.kr.
authors.forename: Teo Jeon
authors.initials: TJ
authors.lastname: Shin
authors.affiliation: Department of Pediatric Dentistry & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea. Electronic address: hege1@snu.ac.kr.
authors.forename: Hong-Keun
authors.initials: HK
authors.lastname: Hyun
authors.affiliation: Department of Pediatric Dentistry & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea. Electronic address: musso@snu.ac.kr.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Cell and Developmental Biology & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea. Electronic address: zang1959@snu.ac.kr.
authors.forename: Zang Hee
authors.initials: ZH
authors.lastname: Lee
authors.affiliation: Department of Pediatric Dentistry & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea; Department of Molecular Genetics & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea. Electronic address: pedoman@snu.ac.kr.
authors.forename: Jung-Wook
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000567:Amelogenesis Imperfecta / Q000000981:diagnostic imaging / Q000235:genetics*; D053523:Amelogenin / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011862:Radiography, Panoramic; D056910:Republic of Korea
chemical_list: C507199:AMELX protein, human; D053523:Amelogenin
keywords: AMELX; Amelogenesis imperfecta; Enamel; Pre-mRNA splicing; X-linked