English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Familial tooth agenesis (FTA), distinguished by developmental failure of selected teeth, is one of the most prevalent craniofacial anomalies in humans. Mutations in genes involved in WNT/β-catenin signaling, including  AXIN2   WNT10A ,  WNT10B ,  LRP6 , and  KREMEN1,  are known to cause FTA. However, mutational interactions among these genes have not been fully explored. In this study, we characterized four FTA kindreds with  LRP6  pathogenic mutations: p.(Gln1252*), p.(Met168Arg), p.(Ala754Pro), and p.(Asn1075Ser). The three missense mutations were predicted to cause structural destabilization of the LRP6 protein. Two probands carrying both an  LRP6  mutant allele and a  WNT10A  variant exhibited more severe phenotypes, suggesting mutational synergism or digenic inheritance. Biallelic  LRP6  mutations in a patient with many missing teeth further supported the dose-dependence of  LRP6 -associated FTA. Analysis of 21 FTA cases with 15 different  LRP6  loss-of-function mutations revealed high heterogeneity of disease severity and a distinctive pattern of missing teeth, with maxillary canines being frequently affected. We hypothesized that various combinations of sequence variants in WNT-related genes can modulate WNT signaling activities during tooth development and cause a wide spectrum of tooth agenesis severity, which highlights the importance of exome/genome analysis for the genetic diagnosis of FTA in this era of precision medicine.

Synergistic Mutations of LRP6 and WNT10A in Familial Tooth Agenesis