Tumor protein 63, encoded by TP63, has an essential role in epidermal differentiation and ectodermal development. Autosomal dominant mutations in human TP63 result in several overlapping syndromes, with some established genotype-phenotype correlations based on the protein domain affected. Several groups have linked TP63-associated ectodermal dysplasia (ED) syndromes with varying degrees of immune dysfunction. In this study, we followed the clinical course of a daughter and father who presented with mild ED symptoms, chronic mucocutaneous candidiasis (CMC), recurrent bacterial infections, and equivocal immune function status. Whole-exome sequencing (WES) and whole-transcriptome analysis via RNA sequencing (RNA-Seq) disclosed a recurrent monoallelic mutation in TP63. Additionally, RNA-Seq data was used for detection of non-albicans Candida species, Candida auris and Candida parapsilosis, in CMC lesions of the daughter and father, respectively. Although a strong association between ED and TP63 mutations exists, the mechanism of immune dysregulation remains unclear. Our cases attest to the variable expressivity of TP63-associated disorders and the potential role of TP63 in maintaining immune system integrity. Furthermore, this study represents the first case of CMC caused by the multidrug-resistant pathogen C. auris in the context of TP63-associated ED and demonstrates the utility of RNA-Seq for concomitant mutation detection and accurate identification of rare and often misidentified pathogens.

ESDR310 - Metatranscriptomics detects emerging multidrug-resistant Candida auris in a family with a mild TP63-associated ectodermal dysplasia

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.