ABSENCE OF CHROMOSOME FRAGILITY AT 19Q13.3 IN PATIENTS WITH MYOTONIC-DYSTROPHY

Myotonic dystrophy (DM) is an autosomal dominant disorder characterize d by a trinucleotide (AGC) amplification at 19q13.3. The degree of tri nucleotide amplification may increase in successive generations and ge nerally correlates with severity of the disorder. Because amplificatio n of a trinucleotide repeat is also associated with the observation of a fra(X)(q27.3) in the fragile X syndrome, we investigated whether ch romosome fragility at 19q13.3 might be inducible in patients with DM. Using 3 different culture stress systems (medium 199, RPMI 1640 with e xcess TdR, and RPMI 1640 with FudR) and high resolution chromosome ana lyses, we studied 6 individuals with DM and 5 unaffected relatives rep resenting two unrelated families. Molecular studies were done on two o f the most affected patients and showed AGC repeat sequences of 970 an d 1,260 at 19q13.3. The normal range of AGC repeat is 5 to 30. We foun d no indication of fragility at 19q13.3 in any of these individuals.