Hypomaturation Amelogenesis Imperfect Caused by a Missense Mutation in ODAM

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. The intracellular localization and secretion of wild-type and mutant ODAM were evaluated by transient transfection and western blotting.
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. No difference in the expression pattern in the nucleus or cytoplasm between wild-type and mutant ODAM fused to GFP was found. The result of western blotting revealed that the secretion of the mutant ODAM was greatly increased compared with the wild-type protein.
Conclusions: For the first time, it is demonstrated that AI is associated with mutation in ODAM. What we found supports a key role for ODAM during enamel biomineralization.