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

Oral Dis. 2017 Sep;23(6):795-800. doi: 10.1111/odi.12663. Epub 2017 Apr 3.

Abstract

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.

Keywords: GJA1; enamel hypoplasia; mutation; novel; oculodentodigital.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • Connexin 43 / genetics*
  • Craniofacial Abnormalities / genetics*
  • Dental Enamel Hypoplasia / genetics*
  • Exome Sequencing
  • Eye Abnormalities / genetics*
  • Foot Deformities, Congenital / genetics*
  • Humans
  • Male
  • Mutation, Missense
  • Pedigree
  • Syndactyly / genetics*
  • Tooth Abnormalities / genetics*

Substances

  • Connexin 43
  • GJA1 protein, human

Supplementary concepts

  • Oculodentodigital Dysplasia