Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy

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Abstract
MYOTONIC dystrophy (DM) is the most common form of adult muscular dystrophy, with a prevalence of 2–14 per 100,000 individuals1. The disease is characterized by progressive muscle weakness and sustained muscle contraction, often with a wide range of accompanying symptoms. The age at onset and severity of the disease show extreme variation, both within and between families. Despite its clinical variability, this dominant condition segregates as a single locus at chromosome 19ql3.3 in every population studied1. It is flanked by the tightly linked genetic markers ERCC1 proximally2,3 and D19S51 distally 4,5; these define the DM critical region. We report the isolation of an expressed sequence from this region which detects a DNA fragment that is larger in affected individuals than in normal siblings or unaffected controls. The size of this fragment varies between affected siblings, and increases in size through generations in parallel with increasing severity of the disease. We postulate that this unstable DNA sequence is the molecular feature that underlies DM.