Original Article
Subject Category: Genetics
Journal of Investigative Dermatology (2008) 128, 2815–2819; doi:10.1038/jid.2008.143; published online 19 June 2008
Immunofluorescence Analysis of Villous Trophoblasts: A Tool for Prenatal Diagnosis of Inherited Epidermolysis Bullosa with Pyloric Atresia
Marina D'Alessio1, Giovanna Zambruno1, Alexandra Charlesworth2,3, Jean-Philippe Lacour2,3,4 and Guerrino Meneguzzi2,3
- 1Laboratory of Molecular and Cell Biology, Immacolata Dermatological Hospital, IDI-IRCCS, Rome, Italy
- 2INSERM U634, Nice, France
- 3University of Nice-Sophia Antipolis, Nice, France
- 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
6
4 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
6
4 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
6
4 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.
Abbreviations:
DEB, dystrophic epidermolysis bullosa; EB, epidermolysis bullosa; EBS, epidermolysis bullosa simplex; JEB, junctional epidermolysis bullosa; PA-EBS, EBS with pyloric atresia; PA-JEB, JEB with pyloric atresia
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
A Novel Homozygous Mutation Affecting Integrin α6 in a Case of Junctional Epidermolysis Bullosa with Pyloric Atresia Detected In Utero by Ultrasound ExaminationJournal of Investigative Dermatology Letter
LAD-1 Is Absent in a Subset of Junctional Epidermolysis Bullosa PatientsJournal of Investigative Dermatology Original Article
Identification of a Lethal Form of Epidermolysis Bullosa Simplex Associated with a Homozygous Genetic Mutation in PlectinJournal of Investigative Dermatology Original Article
Cell cycle and adhesion defects in mice carrying a targeted deletion of the integrin β4 cytoplasmic domainThe EMBO Journal Article (15 Jul 1998)
See all 52 matches for Research


