Study Suggests Link Between Muscular Dystrophy and Epidermolysis Bullosa (EB)

Researchers from Jefferson Medical College, in collaboration with investigators from the United Kingdom, have cloned and sequenced a gene which underlies a subtype of epidermolysis bullosa (EB), a severe, inherited blistering skin disease, and which is associated with late-onset muscular dystrophy. These findings were published in the August 1 issue of Nature Genetics.

The findings suggest that a defect or deficiency in plectin, one of the proteins involved in anchoring skin layers, appears to underlie EB and muscular dystrophy. According to Jouni Uitto, MD, PhD, professor and chairman of the department of dermatology and cutaneous biology at Jefferson, the study results are significant because they demonstrate that EB affects muscle in addition to the layers of skin. The new information will allow for early diagnosis of muscular dystrophy in infants born with skin blistering as well as provide DNA-based prenatal testing for the disease.

Study focused on four families
The study focused on four families with members born with EB and who later developed muscular dystrophy in the second decade of life. At birth, these patients were noted to have skin blisters characteristic of EB. Years later they complained of muscle weakness. Without scientific evidence, a relationship between EB and muscular dystrophy could only be considered coincidental. "Our study was designed to see if there was a connection between epidermolysis bullosa and muscular dystrophy," explained Dr. Uitto. "Study results lead us to believe that EB is a warning sign, of muscular dystrophy in some people rather than an unrelated disorder."

By studying patients with the autosomal recessive disorder epidermolysis bullosa with muscular dystrophy (EB-MD), researchers found that plectin is absent in these people. The absence of plectin suggests that it is the candidate gene/protein system for EB-MD mutation and led investigators to clone and sequence the human plectin cDNA.

Study adds to EB knowledge, broadens genetic testing
As a result of the research findings, women who have a child with EB-MD are eligible for prenatal testing via chorionic villi sampling (CVS), during the ninth week of their subsequent pregnancies.

"The implications of this study are far-reaching," commented Dr. Uitto. "Not only have we added to our growing knowledge of the origins of EB, but we have also broadened the scope of genetic testing."

The research study was truly a multinational effort, joining the talents of Jefferson researchers and investigators from the University of Dundee, Dundee; St. John's Institute of Dermatology, London; Queen Mary & Westfield College, London; ICRF Clare Hall Laboratories, Hertfordshire; University of Marburg, Marburg; Citta University, Catania; St. Luke's Hospital, Malta; Nagoya University, Nagoya; Vienna Biocenter, Vienna.

Dr. Uitto's contributions to this multinational effort follow years of devotion to studying EB. In 1991, his efforts helped identify a collagen gene responsible for holding skin together and linked a site on the gene to a form of EB. This discovery and the research leading up to it provided a solid foundation for the EB-MD study.