A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis

Nuriye Dinckan, Renqian Du, Zeynep C. Akdemir, Yavuz Bayram, Shalini N. Jhangiani, Harsha Doddapaneni, Jianhong Hu, Donna M. Muzny, Yeliz Guven, Oya Aktoren, Hulya Kayserili, Eric Boerwinkle, Richard A. Gibbs, Jennifer E. Posey, James R. Lupski, Zehra O. Uyguner, Ariadne Letra

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Abstract

Tooth development is regulated by multiple genetic pathways, which ultimately drive the complex interactions between the oral epithelium and mesenchyme. Disruptions at any time point during this process may lead to failure of tooth development, also known as tooth agenesis (TA). TA is a common craniofacial abnormality in humans and represents the failure to develop one or more permanent teeth. Many genes and potentially subtle variants in these genes contribute to the TA phenotype. We report the clinical and genetic impact of a rare homozygous ANTXR1 variant (c.1312C>T), identified by whole exome sequencing (WES), in a consanguineous Turkish family with TA. Mutations in ANTXR1 have been associated with GAPO (growth retardation, alopecia, pseudoanodontia, and optic atrophy) syndrome and infantile hemangioma, however no clinical characteristics associated with these conditions were observed in our study family. We detected the expression of Antxr1 in oral and dental tissues of developing mouse embryos, further supporting a role for this gene in tooth development. Our findings implicate ANTXR1 as a candidate gene for isolated TA, suggest the involvement of specific hypomorphic alleles, and expand the previously known ANTXR1-associated phenotypes.

LanguageEnglish
JournalAmerican Journal of Medical Genetics, Part A
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Tooth
Phenotype
Genes
Craniofacial Abnormalities
anthrax toxin receptors
Exome
Mesoderm
Hemangioma
Embryonic Structures
Epithelium
Alleles
Mutation

Keywords

  • ANTXR1
  • Expression
  • Tooth agenesis
  • Whole exome sequencing

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Dinckan, N., Du, R., Akdemir, Z. C., Bayram, Y., Jhangiani, S. N., Doddapaneni, H., ... Letra, A. (Accepted/In press). A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis. American Journal of Medical Genetics, Part A. https://doi.org/10.1002/ajmg.a.38625

A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis. / Dinckan, Nuriye; Du, Renqian; Akdemir, Zeynep C.; Bayram, Yavuz; Jhangiani, Shalini N.; Doddapaneni, Harsha; Hu, Jianhong; Muzny, Donna M.; Guven, Yeliz; Aktoren, Oya; Kayserili, Hulya; Boerwinkle, Eric; Gibbs, Richard A.; Posey, Jennifer E.; Lupski, James R.; Uyguner, Zehra O.; Letra, Ariadne.

In: American Journal of Medical Genetics, Part A, 01.01.2018.

Research output: Contribution to journalArticle

Dinckan, N, Du, R, Akdemir, ZC, Bayram, Y, Jhangiani, SN, Doddapaneni, H, Hu, J, Muzny, DM, Guven, Y, Aktoren, O, Kayserili, H, Boerwinkle, E, Gibbs, RA, Posey, JE, Lupski, JR, Uyguner, ZO & Letra, A 2018, 'A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis' American Journal of Medical Genetics, Part A. https://doi.org/10.1002/ajmg.a.38625
Dinckan, Nuriye ; Du, Renqian ; Akdemir, Zeynep C. ; Bayram, Yavuz ; Jhangiani, Shalini N. ; Doddapaneni, Harsha ; Hu, Jianhong ; Muzny, Donna M. ; Guven, Yeliz ; Aktoren, Oya ; Kayserili, Hulya ; Boerwinkle, Eric ; Gibbs, Richard A. ; Posey, Jennifer E. ; Lupski, James R. ; Uyguner, Zehra O. ; Letra, Ariadne. / A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis. In: American Journal of Medical Genetics, Part A. 2018.
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