A Novel AMELX Mutation, Its Phenotypic Features, and Skewed X Inactivation

Amelogenesis imperfecta (AI) is a group of genetic disorders of defective dental enamel. Mutation of AMELX encoding amelogenin on the X chromosome is a major cause of AI. Here we report a Chinese family with hypoplastic and hypomineralized AI. Whole exome analysis revealed a novel mutation c.185delC...

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Bibliographic Details
Published in:Journal of dental research 2019-07, Vol.98 (8), p.870-878
Main Authors: Duan, X., Yang, S., Zhang, H., Wu, J., Zhang, Y., Ji, D., Tie, L., Boerkoel, C.F.
Format: Article
Language:English
Subjects:
Amelogenesis imperfecta
Androgen receptors
Chromosomes
Dental enamel
Dentin
Dentistry
Deoxyribonucleic acid
DNA
DNA methylation
Enamel
Enzymes
Females
Genes
Genetic disorders
Mutation
Parents & parenting
Peripheral blood
Phenotypic variations
Polymerase chain reaction
Teeth
X chromosomes
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Summary:Amelogenesis imperfecta (AI) is a group of genetic disorders of defective dental enamel. Mutation of AMELX encoding amelogenin on the X chromosome is a major cause of AI. Here we report a Chinese family with hypoplastic and hypomineralized AI. Whole exome analysis revealed a novel mutation c.185delC in exon 5 of AMELX causing the frame shift p.Pro62ArgfsTer47 (or p.Pro62Argfs*47). By sequencing of polymerase chain reaction products and T-vector clones, the mutation was confirmed as homozygous in the proband, hemizygous in her father, and heterozygous in her mother. The proband and her father had small and yellowish teeth with thin and rough enamel that was radiographically indistinguishable from the underlying dentin. Scanning electronic microscopy of 1 maternal tooth showed cracks and exposed loosely packed enamel prisms in affected areas. Consistent with a 25:75 skewing of X inactivation in the peripheral blood DNA as measured by androgen receptor allele methylation, the surface of the mother’s tooth had alternating vertical ridges of transparent normal and white chalky enamel in a 34:66 ratio. In summary, this study provides one of the few phenotypic comparisons of hemizygous and homozygous AMELX mutations and suggests that the skewing of X inactivation in AI contributes to the phenotypic variations in heterozygous carriers of X-linked AI.
ISSN:0022-0345
1544-0591
DOI:10.1177/0022034519854973