Enamelin mutations for dominant and recessive forms of amelogenesis imperfecta

Objectives: The aim of this study was to identify genetic mutations etiologic for amelogenesis imperfecta. Methods: Ten Turkish families segregating for amelogenesis imperfecta (AI) were identified through proband ascertainment. Available family members were examined to identify those with AI. DNA was isolated and genotyping performed to evaluate evidence for genetic linkage to candidate genes including enamelin, KLK4 and MMP20. Direct DNA sequencing to identify gene mutations was performed using ABI Big Dye terminator chemistry. Results: Three different exon 9 enamelin gene mutations were found to be responsible for AI in 2 families. In one family, 2 different ENAM mutations (g.13185-13182 insAG and g.12946-12947ins21bp) were found to cause enamel pitting in the heterozygous state, and in the compound heterozygous state, these mutations caused amelogenesis imperfecta with openbite. Another exon 9 ENAM mutation (g.12662C>A) introduced a premature stop codon. In this family, AI segregated as a dominant trait, consistent with complete penetrance. Testing of 100 controls found that these mutations did not occur in the control population. Conclusions: These findings confirm ENAM mutations can cause AI in dominant and recessive fashions, and the clinical phenotype for some ENAM mutations is dose dependent.