A rare genetic disorder that causes extremely fragile skin and mucosa can be easily diagnosed in a first trimester fetus thanks to a non invasive immunofluorescence procedure. Epidermolysis bullosa with pyloric atresia (PA-EB) is an inherited disorder often resulting in early demise after birth, due to blistering of skin and mucosal membranes and obstruction of the pylorus, the passage linking the stomach and the intestine. Online in the Journal of Investigative Dermatology, researchers describe a test that can help parents assess the risks of bringing their fetus to full term.
Severe forms of PA-EB are characterized by mutations in the genes encoding two proteins, plectin and its interactor, integrin alpha6beta4. Using immunofluorescence, Marina D'Alessio and colleagues found strong expression of these proteins in the first trimester to the end of pregnancy in normal pregnancies, and absent expression in fetuses with PA-JEB. Genetic analysis of both affected and healthy-carrier fetuses identified fourteen gene mutations being responsible for impairing the involved proteins, of which seven are previously unreported.
The team believes their new is test safe for fetuses, as well as easy and accessible to laboratories equipped for immunohistological analyses. Prenatal diagnoses based on protein detection, such as immunofluorescence or proteomic analyses, are useful when DNA-based diagnoses are unavailable. Looking onward, similar procedures might be devised for diagnosing other conditions, such as epidermolysis bullosa with muscular dystrophy, which is similarly linked to genetic mutations in plectin.
Guerrino Meneguzzi (University of Nice-Sophia Antipolis, Nice, France)
Abstract available online.
(C) Journal of Investigative Dermatology press release.
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