2. Academic Validation
  3. Recessive Mutations in ACPT, Encoding Testicular Acid Phosphatase, Cause Hypoplastic Amelogenesis Imperfecta

Recessive Mutations in ACPT, Encoding Testicular Acid Phosphatase, Cause Hypoplastic Amelogenesis Imperfecta

  • Am J Hum Genet. 2016 Nov 3;99(5):1199-1205. doi: 10.1016/j.ajhg.2016.09.018.
Figen Seymen 1,  Youn Jung Kim 2,  Ye Ji Lee 3,  Jenny Kang 3,  Tak-Heun Kim 4,  Hwajung Choi 4,  Mine Koruyucu 1,  Yelda Kasimoglu 1,  Elif Bahar Tuna 1,  Koray Gencay 1,  Teo Jeon Shin 3,  Hong-Keun Hyun 3,  Young-Jae Kim 3,  Sang-Hoon Lee 3,  Zang Hee Lee 5,  Hong Zhang 6,  Jan C-C Hu 6,  James P Simmer 6,  Eui-Sic Cho 7,  Jung-Wook Kim 8
Affiliations

Affiliations

  • 1 Department of Pedodontics, Faculty of Dentistry, Istanbul University, Istanbul 34093, Turkey.
  • 2 Department of Molecular Genetics and the Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
  • 3 Department of Pediatric Dentistry and the Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
  • 4 Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, School of Dentistry, Chonbuk National University, Jeonju 54896, Korea.
  • 5 Department of Cell and Developmental Biology and the Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
  • 6 Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, 1210 Eisenhower Place, Ann Arbor, MI 48108, USA.
  • 7 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.
  • 8 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.
PMID: 27843125 DOI: 10.1016/j.ajhg.2016.09.018
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.

Keywords

ACPT; amelogenesis imperfecta; autosomal-recessive; hypoplastic amelogenesis imperfecta; testicular acid phosphatase.

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