A novel GJA1 mutation in oculodentodigital dysplasia with extensive loss of enamel

Objective: To characterize clinical features and identify genetic causes of a patient with oculodentodigital dysplasia (ODDD). Subjects and methods: Clinical, dental, radiological features were obtained. DNA was collected from an affected Thai family. Whole-exome sequencing was employed to identify the disease-causing mutation causing ODDD. The presence of the identified variant was confirmed by Sanger sequencing. Results: The proband suffered with extensive enamel hypoplasia, polysyndactyly and clinodactyly of the 3rd-5th fingers, microphthalmia, and unique facial characteristics of ODDD. Mutation analysis revealed a novel missense mutation, c. 31C>A, p.L11I, in the GJA1 gene which encodes gap junction channel protein connexin 43. Bioinformatics and structural modeling suggested the mutation to be pathogenic. The parents did not harbor the mutation. Conclusions: This study identified a novel de novo mutation in the GJA1 gene associated with severe tooth defects. These results expand the mutation spectrum and understanding of pathologic dental phenotypes related to ODDD.