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WNT 10A mutation results in severe tooth agenesis in a family of three sisters
Author(s) -
Abid M. F.,
Simpson M. A.,
Barbosa I. A.,
Seppala M.,
Irving M.,
Sharpe P. T.,
Cobourne M. T.
Publication year - 2018
Publication title -
orthodontics and craniofacial research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 55
eISSN - 1601-6343
pISSN - 1601-6335
DOI - 10.1111/ocr.12231
Subject(s) - sanger sequencing , biology , genetics , nonsense mutation , phenotype , exome sequencing , mutation , agenesis , in situ hybridization , exon , gene , wnt signaling pathway , zebrafish , missense mutation , gene expression
Structured Abstract Objectives To identify the genetic basis of severe tooth agenesis in a family of three affected sisters. Patients and Methods A family of three sisters with severe tooth agenesis was recruited for whole‐exome sequencing to identify potential genetic variation responsible for this penetrant phenotype. The unaffected father was tested for specific mutations using Sanger sequencing. Gene discovery was supplemented with in situ hybridization to localize gene expression during human tooth development. Results We report a nonsense heterozygous mutation in exon 2 of WNT 10A c.321C>A[p.Cys107*] likely to be responsible for the severe tooth agenesis identified in this family through the creation of a premature stop codon, resulting in truncation of the amino acid sequence and therefore loss of protein function. In situ hybridization showed expression of WNT 10A in odontogenic epithelium during the early and late stages of human primary tooth development. Conclusions WNT 10A has previously been associated with both syndromic and non‐syndromic forms of tooth agenesis, and this report further expands our knowledge of genetic variation underlying non‐syndromic forms of this condition. We also demonstrate expression of WNT 10A in the epithelial compartment of human tooth germs during development.