Work

Modeling AEC—New approaches to study rare genetic disorders

Year: 2014

Type: review

Abstract: Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare monogenetic disorder that is characterized by severe abnormalities in ectoderm-derived tissues, such as skin and its appendages. A major cause of morbidity among affected infants is severe and chronic skin erosions. Currently, supportive care is the only available treatment option for AEC patients. Mutations in TP63, a gene that encodes key regulators of epidermal development, are the genetic cause of AEC. However, it is currently not clear how mutations in TP63 lead to the various defects seen in the patients' skin. In this review, we will discuss current knowledge of the AEC disease mechanism obtained by studying patient tissue and genetically engineered mouse models designed to mimic aspects of the disorder. We will then focus on new approaches to model AEC, including the use of patient cells and stem cell technology to replicate the disease in a human tissue culture model. The latter approach will advance our understanding of the disease and will allow for the development of new in vitro systems to identify drugs for the treatment of skin erosions in AEC patients. Further, the use of stem cell technology, in particular induced pluripotent stem cells (iPSC), will enable researchers to develop new therapeutic approaches to treat the disease using the patient's own cells (autologous keratinocyte transplantation) after correction of the disease-causing mutations.

Source: American Journal of Medical Genetics Part A

DOI: 10.1002/ajmg.a.36455

Authors: Peter J. Koch, Jason Dinella, Mary Fete, Elaine C. Siegfried, Maranke I. Koster

Institutions: University of Colorado Anschutz, University of Colorado Denver, National Foundation for Ectodermal Dysplasias, Saint Louis University

Language: English

Topic: Genetic and rare skin diseases.

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Foundation for Ectodermal Dysplasias, National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Advancing Translational Sciences