WNT10B mutations associated with isolated dental anomalies

Area of Science:

• Genetics
• Developmental Biology
• Oral Health

Background:

• Isolated hypodontia, a common human malformation, is frequently caused by heterozygous variants in specific genes.
• Heterozygous WNT10A variants are the most prevalent genetic cause of isolated hypodontia.
• Recent research suggests a link between WNT10B variants and oligodontia, indicating a potential role for this paralog in tooth development.

Purpose of the Study:

• To investigate the role of WNT10B variants in a cohort of Thai families with diverse isolated dental anomalies.
• To identify novel genetic causes of tooth agenesis beyond previously known genes.

Main Methods:

• Conducted mutational analysis in 256 unrelated Thai families presenting with isolated dental anomalies.
• Performed whole exome sequencing on patients identified with WNT10B mutations.
• Screened for variants in established hypodontia-associated genes, including WNT10A, MSX1, and PAX9.

Main Results:

• Identified four heterozygous missense variants in WNT10B in seven families with dental anomalies.
• Two specific variants, c.475G>C [p.(Ala159Pro)] and c.1052G>A [p.(Arg351His)], were found to be strongly associated with the observed phenotypes.
• No mutations were detected in other known hypodontia-associated genes in patients with WNT10B mutations.
• WNT10B variants were associated with a spectrum of dental anomalies, including oligodontia, isolated tooth agenesis, microdontia, short tooth roots, dental pulp stones, and taurodontism.

Conclusions:

• WNT10B variants are a significant cause of isolated tooth agenesis and other dental anomalies, extending beyond oligodontia.
• The identified WNT10B variants, p.(Ala159Pro) and p.(Arg351His), are likely causative of these developmental defects.
• This study expands the known genetic basis of tooth agenesis and highlights WNT10B as a key gene in dental development.