The genetic defect in myotonic muscular dystrophy (MMD) is an expanded triplet repeat section of DNA on chromosome 19. MDA-backed researchers were among those who found the defect late in 1991.

The announcement that the long search for the genetic basis of myotonic dystrophy was over came in early 1992 amid great rejoicing, but the fanfare may have been premature. Five years of subsequent study have failed to reveal the precise biological mechanisms underlying myotonic dystrophy, although an enzyme now called myotonin protein kinase and its gene, DMPK, have come under close scrutiny. So far, research hasn't proven that levels of this enzyme are consistently up or down in the cells of those with the disorder. (Investigations have found both, in different patients and in different tissues.) Finding a biochemical abnormality caused by a genetic defect is usually the first step in treatment design.

Now, MDA-supported researcher Dr. Stephen Tapscott at Fred Hutchinson Cancer Center in Seattle, and Drs. Richard Moxley and Charles Thornton, MDA clinic co-directors and researchers at the University of Rochester (N.Y.), are among investigators who have found that there is another gene affected by the expanded CTG repeat section. The gene, known as DMAHP, for dystrophia myotonica homeobox protein, may play an equal or possibly more important role than DMPK in the process underlying myotonic dystrophy, which affects muscle and several other tissues.

"This paper does not in any way imply that the DMPK gene (myotonin) is not relevant," Tapscott said. "Rather, we show that the expanded repeat alters expression of the DMAHP gene and suggest that some of the phenotype [symptoms] of myotonic dystrophy may be caused by suppression of DMAHP expression. In this regard, myotonic dystrophy may be a disease caused by effects on more than one gene and represent a contiguous gene syndrome. How many genes may be involved remains to be determined."

The Rochester researchers and Tapscott's group both published articles in the August 1997 issue of Nature Genetics.