A Missense Mutation in ODAM Causes Autosomal-dominant Hypomaturation Amelogenesis Imperfecta

Objectives: Amelogenesis imperfecta (AI) is a heterogeneous group of rare genetic diseases that affect the normal formation/mineralization of dental enamel and are typically transmitted according to Mendelian inheritance patterns. This study was aimed to search for disease-causing mutations in Chinese families with AI.
Methods: We identified a non-consanguineous Chinese family segregating autosomal-dominant hypomaturation AI without any other health problems. Genomic DNA from 2 affected and 2 unaffected family members were subjected to whole-exome sequencing.
Results: A heterozygous mutation (c.17T>C, p.L6P) in the signal peptide-encoding region of ODAM gene was revealed, which is the only variant that segregates with the disease phenotype in the pedigree, and is predicted to be pathogenic by 4 bioinformatic prediction programmes (MutationTaster, SIFT, Blosum62 and Provean).
Conclusions: Odontogenic ameloblast-associated protein (ODAM) is an ameloblast-secreted protein recently found to be specifically expressed by ameloblasts during the maturation stage of enamel formation. This is the first report of human AI case due to a ODAM mutation, which supports a key role for ODAM during enamel biomineralization.