Effect of the [CCTG]n repeat expansion on ZNF9 expression in myotonic dystrophy type II (DM2)

Myotonic dystrophy is caused by two different mutations: a (CTG)(n) expansion in 3' UTR region of the DMPK gene (DM1) and a (CCTG)(n) expansion in intron 1 of the ZNF9 gene (DM2). The most accredited mechanism for DM pathogenesis is an RNA gain-of-function. Other findings suggest a contributory role of DMPK-insufficiency in DM2. To address the issue of ZNF9 role in DM2. we have analyzed the effects of (CCTG)(n) expansion on ZNF9 expression in lymphoblastoid cell lines (n = 4) from DM2 patients. We did not observe any significant alteration in ZNF9 mRNA and protein levels, as shown by QRT-PCR and Western blot analyses. Additional RT-PCR experiments demonstrated that ZNF9 pre-mRNA splicing pattern, which includes two isoforms, is unmodified in DM2 cells. Our results indicate that the (CCTG)(n) expansion in the ZNF9 intron does not appear to have a direct consequence on the expression of the gene itself. (c) 2005 Elsevier B.V. All rights reserved.