1. ¹Laboratory of Molecular and Cell Biology, Immacolata Dermatological Hospital, IDI-IRCCS, Rome, Italy
2. ²INSERM U634, Nice, France
3. ³University of Nice-Sophia Antipolis, Nice, France
4. ⁴Department of Dermatology, Nice University Hospital, Nice, France

Correspondence: Guerrino Meneguzzi, INSERM U634, University of Nice-Sophia Antipolis, 06107, Nice Cedex 2, France. E-mail: meneguzz@unice.fr

Received 7 February 2008; Revised 3 April 2008; Accepted 6 April 2008; Published online 19 June 2008.

Abstract

Genetic mutations invalidating the genes for integrin 64 and, in some cases, plectin are associated with junctional and simplex epidermolysis bullosa with pyloric atresia (PA-JEB and PA-EBS), respectively. These recessive inherited conditions are characterized by pregnancies with fetal bullae, pyloric atresia, polyhydramnios, and neonatal mucocutaneous blistering, which often results in early postnatal demise. To date, first-trimester DNA-based prenatal diagnosis is not applicable to affected kindred carrying as yet unidentified genetic mutations. Here, we show that first-trimester chorionic villi strongly express both integrin 64 and plectin, which persist throughout the pregnancy. Based on this observation, we implemented 25 prenatal diagnoses in kindred at risk for PA-EB by immunomapping, which identified three PA-JEB-affected fetuses and 22 healthy ones. In 19 cases, including the three PA-JEB pregnancies that were prematurely terminated, the results were confirmed by chorionic villous DNA-based tests, which also led to the identification of seven previously unreported mutations in the 64 integrin genes. Our prediction was further sustained by the birth of 22 healthy babies. These results validate chorionic villi immunofluorescence examination as a tool for prenatal diagnosis of PA-JEB and PA-EBS and indicate that this procedure could be devised for EB with muscular dystrophy, which is also associated with genetic mutations in plectin.