WDR72 Mutations Associated with Amelogenesis Imperfecta and Acidosis

Area of Science:

• Genetics
• Biochemistry
• Dentistry

Background:

• Amelogenesis imperfecta (AI) encompasses genetic disorders affecting tooth enamel formation, presenting as isolated or syndromic conditions.
• Determining the full spectrum of genes and mutations causing AI is crucial for accurate genetic diagnosis.
• WDR72 gene defects are known to cause AI type IIA3, an autosomal recessive disorder.

Purpose of the Study:

• To identify and characterize WDR72 gene mutations in families with amelogenesis imperfecta.
• To expand the understanding of WDR72's role in enamel formation and associated syndromic features.
• To improve diagnostic capabilities for WDR72-related AI.

Main Methods:

• Whole exome sequencing was employed to analyze genetic variations in six families presenting with AI.
• Segregation analysis was performed to confirm the link between WDR72 mutations and the enamel phenotype.
• Clinical evaluation included assessment of enamel characteristics, serum pH, and anthropometric measurements.

Main Results:

• Biallelic WDR72 mutations were identified in all six families, including novel stop-gain, missense, and deletion mutations, as well as a previously reported frameshift mutation.
• The identified mutations perfectly segregated with the amelogenesis imperfecta phenotype across generations.
• Three patients exhibited decreased serum pH, suggesting a potential link to renal tubular acidosis, while stature and weight showed variable, non-specific trends.

Conclusions:

• WDR72 mutations are confirmed to cause a syndromic form of amelogenesis imperfecta.
• The findings enhance the genetic diagnostic framework for AI, particularly for WDR72-related defects.
• This study underscores the importance of comprehensive genetic analysis in diagnosing complex dental anomalies.