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

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 autosom...

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Bibliographic Details
Published in:American journal of human genetics 2016-11, Vol.99 (5), p.1199-1205
Main Authors: Seymen, Figen, Kim, Youn Jung, Lee, Ye Ji, Kang, Jenny, Kim, Tak-Heun, Choi, Hwajung, Koruyucu, Mine, Kasimoglu, Yelda, Tuna, Elif Bahar, Gencay, Koray, Shin, Teo Jeon, Hyun, Hong-Keun, Kim, Young-Jae, Lee, Sang-Hoon, Lee, Zang Hee, Zhang, Hong, Hu, Jan C-C., Simmer, James P., Cho, Eui-Sic, Kim, Jung-Wook
Format: Article
Language:English
Subjects:
Acid Phosphatase - genetics
Acid Phosphatase - metabolism
ACPT
amelogenesis imperfecta
Amelogenesis Imperfecta - diagnosis
Amelogenesis Imperfecta - genetics
autosomal-recessive
Child
Dental Enamel - abnormalities
Dental Enamel Proteins - genetics
Dental Enamel Proteins - metabolism
Enamel
Exons
Female
Genes, Recessive
Genetic disorders
Homozygote
Humans
hypoplastic amelogenesis imperfecta
Immunohistochemistry
Male
Mutation
Pedigree
Protein Conformation
Sequence Alignment
Teeth
testicular acid phosphatase
Turkey
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Summary: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.
ISSN:0002-9297
1537-6605
DOI:10.1016/j.ajhg.2016.09.018