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

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2016 Nov 16

PMID 27843125

Citations 28

Authors

Figen Seymen

Youn Jung Kim

Ye Ji Lee

Jenny Kang

Tak-Heun Kim

HwaJung Choi

Mine Koruyucu

Yelda Kasimoglu

Elif Bahar Tuna

Koray Gencay

Teo Jeon Shin

Hong-Keun Hyun

Young-Jae Kim

Sang-Hoon Lee

Zang Hee Lee

Hong Zhang

Jan C-C Hu

James P Simmer

Eui-Sic Cho

Jung-Wook Kim

Affiliations

Soon will be listed here.

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.

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