Diagnosis of Wilson's disease in an asymptomatic sibling by DNA linkage analysis

Gastroenterology. 1995 Dec;109(6):2015-8. doi: 10.1016/0016-5085(95)90771-8.


The molecular genetic diagnosis of Wilson's disease in the 5-year-old sister of a patient with Wilson's disease is reported. The girl was clinically free of disease and had no conventional biochemical markers of Wilson's disease (i.e., normal ceruloplasmin, normal copper in the serum, normal 24-hour urinary copper excretion). Diagnosis with restriction fragment length polymorphisms and a nonradioactive polymerase chain reaction-based analysis with microsatellite markers showed her to be homozygous for the disease-associated markers. A liver biopsy was performed, and a 20-fold increased liver copper content confirmed the diagnosis. The child was treated with chelation therapy with D-penicillamine. The report of this study clearly shows the advantage of DNA linkage analysis (especially polymerase chain reaction) over conventional laboratory methods for presymptomatic diagnosis of Wilson's disease before irreparable liver and neurological damage occurs. The only limitation of this DNA-based diagnosis is the fact that it is only applicable in siblings of an index patient whose diagnosis was made by phenotypic criteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy
  • Child
  • Child, Preschool
  • Copper / analysis
  • DNA / analysis*
  • Family Health
  • Female
  • Genetic Linkage*
  • Hepatolenticular Degeneration / diagnosis*
  • Hepatolenticular Degeneration / genetics
  • Hepatolenticular Degeneration / metabolism
  • Humans
  • Liver / chemistry
  • Liver / pathology
  • Male
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length


  • Copper
  • DNA