Study Suggests Link Between Muscular Dystrophy and Epidermolysis Bullosa
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.