INABILITY TO INDUCE FRAGILE SITES AT CTG REPEATS IN CONGENITAL MYOTONIC-DYSTROPHY

Myotonic dystrophy (DM) is a trinucleotide repeat syndrome which can c ontain 50 to over 2,000 CTG repeats in affected individuals, but does not express a fragile site, Although one prior study [Jalal et al., Am J Med Genet 46:441-443, 1993] did not find evidence of fragility at 1 9q13.3 in six individuals affected with DM using induction protocols f or folate sensitive fragile sites, other chemicals may induce fragile site expression at this site, In an attempt to induce fragile sites at 19q13.3, blood cultures from four congenital DM cases and four contro l individuals treated with fluorodeoxyuridine (folate-sensitive rare f ragile sites), bromodeoxyurdine (rare and common fragile sites), aphid icolin (common fragile sites), and 5-azacytidine (common fragile sites ) were harvested using routine cytogenetic technique. Slides were soli d stained and 100 cells were examined for fragile site expression, par ticularly on F group chromosomes. The latter were photographed prior t o destaining and G-banded to verify chromosome and band location of br eakage. No culture conditions induced a fragile site at band 19q13.3 a t >1% expression in patients with congenital DM. Our results suggest t hat CTG repeats, even when present in >1,000 copies, may behave differ ently from other large expansions which are associated with fragile si tes. The CTG repeats in DM are not associated with a methylated CpG is land, as are folate-sensitive fragile sites, which most Likely plays a role in the expression of fragile sites at the trinucleotide repetiti ve site. (C) 1996 Wiley-Liss, Inc.