Reduction of the DM-associated homeo domain protein (DMAHP) mRNA in different brain areas of myotonic dystrophy patients

Myotonic dystrophy (DM) is a multisystemic disease caused by expansion of a CTG trinucleotide repeat in the 3' untranslated region of the DMPK protein kinase gene on chromosome 19q13.3. The mechanism by which this expansion causes disease remains unknown. It has been suggested that CTG expansion not only affects the expression of the DMPK gene, but also alters the nuclear RNA metabolism and expression of neighboring genes. DMAHP, which is expressed in various human tissues, including skeletal muscle, heart and brain, is immediately distal to the 3' end of DMPK gene, in a CpG island which contains the CTG repeat. Here we report a 4- to 5-fold reduction of the expression of the DMAHP gene in different brain areas of DM patients. Our results demonstrate that [CTG](n) expansion alters the brain DMAHP mRNA expression supporting a dominant-negative effect at the cellular level of DM [CTG](n) mutation. The reduced brain expression of DMAHP could explain cerebral impairment in DM patients. Copyright (C) 1999 Elsevier Science B.V.