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

Abstract

To characterize clinical features and identify genetic causes of a patient with oculodentodigital dysplasia (ODDD). 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. 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. 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.