title: Myotonic dystrophy (DM) protein kinase levels in congenital and adult DM patients.
abstract: Myotonic dystrophy is caused by a (CTG)n trinucleotide repeat expansion located in the 3' untranslated region of the myotonic dystrophy protein kinase gene (DMPK). To date, the disease mechanism has proven elusive. The mutation would not be expected to affect kinase function and yet the disease is inherited in a dominant fashion. Mutant DMPK transcripts have been demonstrated to be retained in affected cell nuclei which could reduce DMPK protein levels and cause disease by haploinsufficiency. An alternate hypothesis is that the expansion confers a toxic gain of function on the transcript. In previous studies, various 52-55 kDa proteins have been detected using antisera targeted against DMPK and a decline of two of these candidates in disease tissues was reported. Current information now suggests that these proteins are not products of the myotonic dystrophy gene. We have characterised an antiserum which has been confirmed to recognise authentic 71 and 80 kDa isoforms of DMPK. Determination of the kinase levels in disease tissues with controls for patient age and tissue integrity demonstrates a modest overexpression in adult patients. In tissues from severely affected congenital patients only a slight decline is seen. This data argues against DMPK haploinsufficiency as a disease mechanism.
authors.affiliation: Soulange Gauthier Karsh Molecular Genetics Laboratory, Children's Hospital of Eastern Ontario, Ottawa, Canada.
authors.forename: M A
authors.initials: MA
authors.lastname: Narang
authors.forename: J D
authors.initials: JD
authors.lastname: Waring
authors.forename: L A
authors.initials: LA
authors.lastname: Sabourin
authors.forename: R G
authors.initials: RG
authors.lastname: Korneluk
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology; D009223:Myotonic Dystrophy / Q000151:congenital / Q000201:enzymology*; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C585517:DMPK protein, human; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases