A Fourth KLK4 Mutation Is Associated with Enamel Hypomineralisation and Structural Abnormalities

Area of Science:

• Genetics
• Biochemistry
• Dental Science

Background:

• Amelogenesis imperfecta (AI) encompasses genetic disorders affecting tooth enamel formation.
• Mutations in the KLK4 gene, crucial for enamel maturation, are known causes of AI.
• This study investigates a novel KLK4 mutation in Pakistani families with autosomal recessive hypomaturation AI.

Purpose of the Study:

• To identify and characterize a new KLK4 gene mutation causing AI.
• To analyze the resulting enamel phenotype using advanced imaging and testing techniques.
• To elucidate the role of KLK4 in enamel mineralization and hardening.

Main Methods:

• Genetic analysis to identify the KLK4 c.632delT mutation in five Pakistani AI families.
• High-resolution computerized X-ray tomography (CT) for enamel structure analysis.
• Scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and microhardness testing (MH) to assess enamel properties.

Main Results:

• The homozygous KLK4 c.632delT mutation was identified in affected individuals.
• KLK4 enamel exhibited hypomineralization, particularly in the inner layer, with reduced calcium and phosphorus content.
• Inner enamel of KLK4 individuals was significantly softer than outer enamel, unlike controls.

Conclusions:

• The KLK4 c.632delT mutation is a likely cause of autosomal recessive AI in the Pakistani population.
• KLK4 is essential for the hardening and mineralization of the inner enamel layer.
• Phenotypic findings in humans mirror those in Klk4 knockout mice, validating KLK4's role.