title: Myotonic dystrophy type 2: molecular, diagnostic and clinical spectrum.
abstract: BACKGROUND
  Myotonic dystrophy types 1 (DM1) and 2 (DM2/proximal myotonic myopathy PROMM) are dominantly inherited disorders with unusual multisystemic clinical features. The authors have characterized the clinical and molecular features of DM2/PROMM, which is caused by a CCTG repeat expansion in intron 1 of the zinc finger protein 9 (ZNF9) gene.
  
  
  METHODS
  Three-hundred and seventy-nine individuals from 133 DM2/PROMM families were evaluated genetically, and in 234 individuals clinical and molecular features were compared.
  
  
  RESULTS
  Among affected individuals 90% had electrical myotonia, 82% weakness, 61% cataracts, 23% diabetes, and 19% cardiac involvement. Because of the repeat tract's unprecedented size (mean approximately 5,000 CCTGs) and somatic instability, expansions were detectable by Southern analysis in only 80% of known carriers. The authors developed a repeat assay that increased the molecular detection rate to 99%. Only 30% of the positive samples had single sizeable expansions by Southern analysis, and 70% showed multiple bands or smears. Among the 101 individuals with single expansions, repeat size did not correlate with age at disease onset. Affected offspring had markedly shorter expansions than their affected parents, with a mean size difference of -17 kb (-4,250 CCTGs).
  
  
  CONCLUSIONS
  DM2 is present in a large number of families of northern European ancestry. Clinically, DM2 resembles adult-onset DM1, with myotonia, muscular dystrophy, cataracts, diabetes, testicular failure, hypogammaglobulinemia, and cardiac conduction defects. An important distinction is the lack of a congenital form of DM2. The clinical and molecular parallels between DM1 and DM2 indicate that the multisystemic features common to both diseases are caused by CUG or CCUG expansions expressed at the RNA level.
authors.affiliation: Institute of Human Genetics, Department of Neurology, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA. johnday@umn.edu
authors.forename: J W
authors.initials: JW
authors.lastname: Day
authors.forename: K
authors.initials: K
authors.lastname: Ricker
authors.forename: J F
authors.initials: JF
authors.lastname: Jacobsen
authors.forename: L J
authors.initials: LJ
authors.lastname: Rasmussen
authors.forename: K A
authors.initials: KA
authors.lastname: Dick
authors.forename: W
authors.initials: W
authors.lastname: Kress
authors.forename: C
authors.initials: C
authors.lastname: Schneider
authors.forename: M C
authors.initials: MC
authors.lastname: Koch
authors.forename: G J
authors.initials: GJ
authors.lastname: Beilman
authors.forename: A R
authors.initials: AR
authors.lastname: Harrison
authors.forename: J C
authors.initials: JC
authors.lastname: Dalton
authors.forename: L P W
authors.initials: LP
authors.lastname: Ranum
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D015139:Blotting, Southern; D002386:Cataract / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D002648:Child; D015897:Comorbidity; D042622:DNA Repeat Expansion / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005799:Genes, Dominant; D005820:Genetic Testing / Q000379:methods*; D005858:Germany / Q000453:epidemiology / Q000208:ethnology; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D009132:Muscles / Q000473:pathology; D009223:Myotonic Dystrophy / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D011044:Poland / Q000208:ethnology; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C433227:CNBP protein, human; D016601:RNA-Binding Proteins; D012313:RNA