Phenotype of ENAM mutations is dosage-dependent

Area of Science:

• Genetics
• Oral Biology
• Developmental Biology

Background:

• Amelogenesis imperfecta (AI) is a group of inherited dental disorders affecting tooth enamel formation.
• Mutations in the ENAM gene, encoding enamelin, are a known cause of hypoplastic AI.
• The spectrum of ENAM-related phenotypes, particularly the dose-dependency, requires further investigation.

Observation:

• This study investigated ENAM gene mutations in ten Turkish families with autosomal hypoplastic AI.
• ENAM mutations were identified in two families, revealing novel and previously described genetic alterations.
• Specific mutations correlated with distinct inheritance patterns and phenotypic severity.

Findings:

• A novel nonsense mutation (p.S246X) in ENAM caused dominant autosomal hypoplastic AI with localized enamel pitting.
• Compound heterozygosity for two insertion mutations in ENAM resulted in autosomal-recessive generalized hypoplastic AI.
• Heterozygous carriers of insertion mutations exhibited a localized enamel-pitting phenotype, suggesting a dose-dependent effect.

Implications:

• These findings confirm ENAM mutations as a significant cause of hypoplastic AI across different populations.
• The study highlights the dose-dependent nature of ENAM mutations, explaining varied phenotypes from localized pitting to severe hypoplasia.
• Understanding genotype-phenotype correlations in ENAM mutations is crucial for genetic counseling and potential therapeutic strategies.