Whole exome sequencing in an Italian family with isolated maxillary canine agenesis and canine eruption anomalies

Ersilia Barbato, Alice Traversa, Rosanna Guarnieri, Agnese Giovannetti, Maria Luce Genovesi, Maria Rosa Magliozzi, Stefano Paolacci, Andrea Ciolfi, Simone Pizzi, Roberto Di Giorgio, Marco Tartaglia, Antonio Pizzuti, Viviana Caputo

Research output: Contribution to journalArticlepeer-review


Objective: The aim of this study was the clinical and molecular characterization of a family segregating a trait consisting of a phenotype specifically involving the maxillary canines, including agenesis, impaction and ectopic eruption, characterized by incomplete penetrance and variable expressivity. Design: Clinical standardized assessment of 14 family members and a whole-exome sequencing (WES) of three affected subjects were performed. WES data analyses (sequence alignment, variant calling, annotation and prioritization) were carried out using an in-house implemented pipeline. Variant filtering retained coding and splice-site high quality private and rare variants. Variant prioritization was performed taking into account both the disruptive impact and the biological relevance of individual variants and genes. Sanger sequencing was performed to validate the variants of interest and to carry out segregation analysis. Results: Prioritization of variants ``by function'' allowed the identification of multiple variants contributing to the trait, including two concomitant heterozygous variants in EDARADD (c.308C > T, p.Ser103Phe) and COL5A1 (c.1588G > A, p.Gly530Ser), specifically associated with a more severe phenotype (Le. canine agenesis). Differently, heterozygous variants in genes encoding proteins with a role in the WNT pathway were shared by subjects showing a phenotype of impacted/ectopic erupted canines. Conclusions: This study characterized the genetic contribution underlying a complex trait consisting of isolated canine anomalies in a medium-sized family, highlighting the role of WNT and EDA cell signaling pathways in tooth development.
Original languageEnglish
Pages (from-to)96-102
Number of pages7
JournalArchives of Oral Biology
Publication statusPublished - Jul 1 2018


  • Canine tooth
  • Tooth eruption
  • Hypodontia
  • Whole exome sequencing
  • WNT signaling pathway


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