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

Dinckan N., DU R., AKDEMIR Z. C., BAYRAM Y., JHANGIANI S. N., DODDAPANENI H., ...More

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, vol.176, no.4, pp.1015-1022, 2018 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 176 Issue: 4
  • Publication Date: 2018
  • Doi Number: 10.1002/ajmg.a.38625
  • Journal Name: AMERICAN JOURNAL OF MEDICAL GENETICS PART A
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1015-1022
  • Keywords: ANTXR1, expression, tooth agenesis, whole exome sequencing, ENDOTHELIAL MARKER 8, GROWTH-RETARDATION, MISSENSE MUTATION, GENETIC-VARIATION, OPTIC ATROPHY, GAPO SYNDROME, ALOPECIA, PATIENT
  • Istanbul University Affiliated: Yes

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.