MINNEAPOLIS / ST. PAUL (August 1, 2001) -- University of Minnesota researchers have pinpointed the gene on chromosome 3 that causes myotonic dystrophy Type 2 (DM2). The findings will be reported in the August 3 issue of Science.
Myotonic dystrophy (DM), the most common form of muscular dystrophy in adults, affects the eyes, heart, hormonal systems and blood, in addition to causing muscular dystrophy and involuntary muscle stiffness (myotonia). Although the genetic change underlying one form of myotonic dystrophy (DM1) was found on chromosome 19 in 1992, scientists have disagreed about how it causes disease. Dr. Laura Ranum, an associate professor in the department of genetics, cell biology and development and the Institute of Human Genetics, and Dr. John W. Day, an associate professor in the department of neurology and the Institute of Human Genetics, have characterized the second form of myotonic dystrophy (DM2) in an effort to clarify the cause of this complex disease. They located the genetic cause of DM2 on chromosome 3 in 1998 (Nature Genetics 19:196), and have collaborated with investigators in Germany and Texas to find the underlying genetic mutation. The new report describes the mutation they found, which indicates that abnormal RNA causes both DM1 and DM2.
"RNA is the messenger molecule that translates the DNA code into proteins," said Ranum. "In the past the focus has been on protein abnormalities as the cause of genetic disorders, and researchers thought that RNA had little or no direct role in causing disease. Our findings indicate that additional research is needed to examine the role of RNA in human disease."
The findings reported in Science indicate that DM2 is caused by an expansion located in intron 1 of the zinc finger protein 9 (ZNF9) gene.
"These results enable us to focus our research and to work towards eliminating this disease for future generations of families," said Day. "But perhaps more importantly, for the first time there is indisputable evidence that RNA itself can cause disease."
Ranum, Day and their colleagues reviewed the clinical and genetic features of nearly 200 individuals from 100 families with DM2. The disorder is quite common in Germany and in Minnesota families, many of which are of German ancestry. The new results will allow the immediate development of a genetic test for DM2 and will eventually lead to a more complete understanding and treatment of this form of muscular dystrophy.