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Modeling AEC—New approaches to study rare genetic disorders
Author(s) -
Koch Peter J.,
Dinella Jason,
Fete Mary,
Siegfried Elaine C.,
Koster Maranke I.
Publication year - 2014
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36455
Subject(s) - induced pluripotent stem cell , disease , medicine , stem cell , mechanism (biology) , genetic disorder , bioinformatics , transplantation , ectoderm , biology , embryonic stem cell , pathology , gene , genetics , surgery , philosophy , epistemology
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. © 2014 Wiley Periodicals, Inc.