title: Recessive Mutations in ACPT, Encoding Testicular Acid Phosphatase, Cause Hypoplastic Amelogenesis Imperfecta.
abstract: Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders affecting tooth enamel. The affected enamel can be hypoplastic and/or hypomineralized. In this study, we identified ACPT (testicular acid phosphatase) biallelic mutations causing non-syndromic, generalized hypoplastic autosomal-recessive amelogenesis imperfecta (AI) in individuals from six apparently unrelated Turkish families. Families 1, 4, and 5 were affected by the homozygous ACPT mutation c.713C>T (p.Ser238Leu), family 2 by the homozygous ACPT mutation c.331C>T (p.Arg111Cys), family 3 by the homozygous ACPT mutation c.226C>T (p.Arg76Cys), and family 6 by the compound heterozygous ACPT mutations c.382G>C (p.Ala128Pro) and 397G>A (p.Glu133Lys). Analysis of the ACPT crystal structure suggests that these mutations damaged the activity of ACPT by altering the sizes and charges of key amino acid side chains, limiting accessibility of the catalytic core, and interfering with homodimerization. Immunohistochemical analysis confirmed localization of ACPT in secretory-stage ameloblasts. The study results provide evidence for the crucial function of ACPT during amelogenesis.
authors.affiliation: Department of Pedodontics, Faculty of Dentistry, Istanbul University, Istanbul 34093, Turkey.
authors.forename: Figen
authors.initials: F
authors.lastname: Seymen
authors.affiliation: Department of Molecular Genetics and the Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Youn Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Pediatric Dentistry and the Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Ye Ji
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Pediatric Dentistry and the Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Jenny
authors.initials: J
authors.lastname: Kang
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, School of Dentistry, Chonbuk National University, Jeonju 54896, Korea.
authors.forename: Tak-Heun
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, School of Dentistry, Chonbuk National University, Jeonju 54896, Korea.
authors.forename: Hwajung
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Pedodontics, Faculty of Dentistry, Istanbul University, Istanbul 34093, Turkey.
authors.forename: Mine
authors.initials: M
authors.lastname: Koruyucu
authors.affiliation: Department of Pedodontics, Faculty of Dentistry, Istanbul University, Istanbul 34093, Turkey.
authors.forename: Yelda
authors.initials: Y
authors.lastname: Kasimoglu
authors.affiliation: Department of Pedodontics, Faculty of Dentistry, Istanbul University, Istanbul 34093, Turkey.
authors.forename: Elif Bahar
authors.initials: EB
authors.lastname: Tuna
authors.affiliation: Department of Pedodontics, Faculty of Dentistry, Istanbul University, Istanbul 34093, Turkey.
authors.forename: Koray
authors.initials: K
authors.lastname: Gencay
authors.affiliation: Department of Pediatric Dentistry and the Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Teo Jeon
authors.initials: TJ
authors.lastname: Shin
authors.affiliation: Department of Pediatric Dentistry and the Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Hong-Keun
authors.initials: HK
authors.lastname: Hyun
authors.affiliation: Department of Pediatric Dentistry and the Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Young-Jae
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Pediatric Dentistry and the Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Cell and Developmental Biology and the Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Zang Hee
authors.initials: ZH
authors.lastname: Lee
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, 1210 Eisenhower Place, Ann Arbor, MI 48108, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, 1210 Eisenhower Place, Ann Arbor, MI 48108, USA.
authors.forename: Jan C-C
authors.initials: JC
authors.lastname: Hu
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, 1210 Eisenhower Place, Ann Arbor, MI 48108, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Simmer
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, School of Dentistry, Chonbuk National University, Jeonju 54896, Korea. Electronic address: oasis@jbnu.ac.kr.
authors.forename: Eui-Sic
authors.initials: ES
authors.lastname: Cho
authors.affiliation: Department of Molecular Genetics and the Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea; Department of Pediatric Dentistry and the Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea. Electronic address: pedoman@snu.ac.kr.
authors.forename: Jung-Wook
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics* / Q000378:metabolism; D000567:Amelogenesis Imperfecta / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D003743:Dental Enamel / Q000002:abnormalities; D003746:Dental Enamel Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D011487:Protein Conformation; D016415:Sequence Alignment; D014421:Turkey
chemical_list: D003746:Dental Enamel Proteins; C000618993:ACP4 protein, human; D000135:Acid Phosphatase
keywords: ACPT; amelogenesis imperfecta; autosomal-recessive; hypoplastic amelogenesis imperfecta; testicular acid phosphatase