Medical sequencing of de novo ectodermal dysplasia in identical twins and evaluation of the potential eligibility for recombinant EDA therapy

Abstract

The purpose of this study was to test two 8-year-old identical twins with ectodermal dysplasia (ED) and their unaffected parents for the presence of mutations in the EDA gene with the hypothesis that they might be carrying a de novo mutation in EDA and potentially eligible for recombinant EDA therapy. DNA was extracted using saliva samples obtained from the identical twin girls and both parents. PCR products of Ectodyplasin A (EDA), Ectodysplasin Receptor (EDAR), Ectodysplasin Receptor Associated Death Domain (EDARADD), and Connexin-30 (GJB6) were sequenced by the Sanger method and the results analyzed using a reference sequence. Exons and exon-intron boundaries of EDA, EDAR, EDARADD, and GJB6 were sequenced in both parents and the affected identical twin pair. No mutations were detected in EDA or GJB6. Genetic variants located in the intron of EDAR were found but determined to be non-contributory to the twins’ ED. A microsatellite polymorphism was detected in all four subjects in exon 4 of the EDARADD gene but determined not to be causal to the ED. There was a silent mutation detected in exon 6 of the EDARADD gene of both the daughters and their unaffected mother but also unlikely to be the cause of ED. These results suggest that ED of the subjects is caused by a de novo mutation in a gene not studied here. It is likely these subjects and their future offspring would not benefit from the development of recombinant EDA replacement therapy.

Keywords: Ectodermal Dysplasia, EDA, Mutation