DM2/PROMM and other myotonic dystrophies

Number 115
Date 14 February 2003

The ENMC consortium on myotonic dystrophy type 2 (=DM2/PROMM) held its 3rd workshop in Naarden, the Netherlands, 14-16th February 2003. It was attended by 22 active participants from Finland, France, Germany, Italy, the Netherlands, Spain, the United Kingdom and the USA. The meeting opened with an overview of the main scientific progress in the molecular genetics since its 2nd workshop held in 2000: The identification of the mutation responsible for the myotonic dystrophy type 2 disease. Participants now reported on the occurrence of the mutation in the previously DM2-linked and unlinked families. The results of these analyses show that all DM2-linked families harbor the same mutation defect, an unusually large CCTG-repeat expansion of the DNA on chromosome 3q21. Morover, all families previously reported as DM2-unlinked PROMM families also proved to have the same CCTG-repeat expansion mutation. The diagnosis does not yet provide possibilities for therapy, but it is of great importance for the patients to correctly understand their symptoms and to get the best possible management. However, the DNA analysis for definite mutation detection is difficult, and not yet largely available as a routine diagnostic procedure. The workshop consortium agreed on sharing methological protocols in order to find the optimal molecular diagnostic procedure. For the routine diagnostic work-up, the identification of muscle fiber type 2 atrophy on muscle biopsy specimens may be helpful in selecting patients for molecular genetic testing. Some new diagnostic methods based on tissue in situ hybridization were also introduced. Much of the workshop was advocated to the next task for the scientific research efforts: the understanding of the abnormal events taking place in the muscles and other affected organs caused and directed by the DM2 mutation, in order to answer scientific questions like: Why is there no detectable correlation between the expansion size of the DM2 mutation and the clinical severity of the disease? Why is the reproductive system so much better protected against the consequences of the DM2 mutation in comparison to myotonic dystrophy type 1 (=Steinert's disease)? The identification of the DM2 mutation has greatly improved the understanding of the basic molecular abnormalities also in Steinert's disease.

An extended report of this meeting is published in Neuromuscular Disorders, Volume 13, No. 7-8, September 2003.

Dr. B. Udd (Finland)
Dr. R. Krahe (U.S.A.)