title: Direct diagnosis of myotonic dystrophy with a disease-specific DNA marker.
abstract: BACKGROUND
  Myotonic dystrophy is the most common inherited form of muscular dystrophy affecting adults. Its symptoms are not confined to muscle, and variability in their nature and in the patient's age at their onset can make diagnosis difficult. A specific unstable DNA sequence associated with myotonic dystrophy has recently been identified. We describe the use of a DNA probe (p5B1.4) that can detect this mutation directly, improving the accuracy and speed of diagnosis.
  
  
  METHODS
  We analyzed DNA extracted from the peripheral-blood lymphocytes of 112 unrelated patients with myotonic dystrophy and their families, using molecular genetic techniques. Southern blot analysis and amplification with the polymerase chain reaction were used to determine the extent of expansion of the unstable DNA sequence.
  
  
  RESULTS
  Probe p5B1.4 allowed direct identification of the myotonic dystrophy mutation in 108 of the 112 unrelated patients. In three families for whom the clinical and genetic data obtained with linked probes were ambiguous, the probe identified persons at risk for symptoms of this disorder and demonstrated that a possible sporadic case of myotonic dystrophy was familial. In one of these families the size of the unstable myotonic dystrophy-specific fragment decreased on transmission to offspring, who remained asymptomatic.
  
  
  CONCLUSIONS
  The diagnosis of myotonic dystrophy is improved by the use of a probe that detects directly the mutation responsible for this disorder.
authors.affiliation: Department of Anatomy, Charing Cross and Westminster Medical School, London, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Shelbourne
authors.forename: J
authors.initials: J
authors.lastname: Davies
authors.forename: J
authors.initials: J
authors.lastname: Buxton
authors.forename: M
authors.initials: M
authors.lastname: Anvret
authors.forename: E
authors.initials: E
authors.lastname: Blennow
authors.forename: M
authors.initials: M
authors.lastname: Bonduelle
authors.forename: E
authors.initials: E
authors.lastname: Schmedding
authors.forename: I
authors.initials: I
authors.lastname: Glass
authors.forename: R
authors.initials: R
authors.lastname: Lindenbaum
authors.forename: R
authors.initials: R
authors.lastname: Lane
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D015342:DNA Probes; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009223:Myotonic Dystrophy / Q000175:diagnosis* / Q000235:genetics; D010375:Pedigree; D010446:Peptide Fragments / Q000032:analysis; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D015342:DNA Probes; D005819:Genetic Markers; D010446:Peptide Fragments