Novel GJA1/Cx43 Variant Associated With Oculo-Dento-Digital Dysplasia Syndrome: Clinical Phenotype and Cellular Mechanisms

Irene Sargiannidou; Violetta Christophidou-Anastasiadou; Andreas Hadjisavvas; George A Tanteles; Kleopas A Kleopa

doi:10.3389/fgene.2020.604806

Novel GJA1/Cx43 Variant Associated With Oculo-Dento-Digital Dysplasia Syndrome: Clinical Phenotype and Cellular Mechanisms

Front Genet. 2021 Jan 27:11:604806. doi: 10.3389/fgene.2020.604806. eCollection 2020.

Authors

Irene Sargiannidou¹, Violetta Christophidou-Anastasiadou^{2

3}, Andreas Hadjisavvas⁴, George A Tanteles², Kleopas A Kleopa^{1

5

6}

Affiliations

¹ Department of Neuroscience, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
² Clinical Genetics Center, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
³ Department of Clinical Genetics, Makarios Hospital, Nicosia, Cyprus.
⁴ Department of Molecular Pathology and Electron Microscopy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
⁵ Center of Neuromuscular Disorders, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
⁶ Center for Multiple Sclerosis and Related Disorders, Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.

Abstract

Oculodentodigital dysplasia syndrome is associated with numerous pathogenic variants in GJA1, the gene encoding connexin43 gap junction protein. A novel in-frame deletion (p.Lys134del) was found in our clinic. The patient showed all the typical dysmorphic features of the syndrome. The functional consequences of this variant were also studied in an in vitro system. Cells expressed significantly less number of gap junction plaques with a great number of them retained intracellularly.

Keywords: GJA1 gene; connexin43; gap junctions; leukodystrophy; oculodentodigital dysplasia.