title: Wilson disease in offspring of affected patients: report of four French families.
abstract: BACKGROUND
  Wilson disease (WD) is an autosomal recessive genetic disorder caused by mutations in the ATP7B gene resulting in toxic accumulation of copper mainly in the liver and brain. Early treatment may prevent irreversible tissue damage.
  
  
  OBJECTIVE
  We report on four families with an occurrence of WD in two consecutive generations in order to highlight the need for screening offspring of affected parents.
  
  
  RESULTS
  In all families, one parent was known to be affected with WD. Screening for the disease was not performed in children from two families until occurrence of liver disease in one and of neurological symptoms in the other. In two other families, screening of children as soon as diagnosis was performed in the affected parent allowed a timely rescue of advanced liver disease in one while two affected children were asymptomatic. In three children, diagnosis required direct sequencing of the ATP7B gene. Two novel disease-causing mutations are reported.
  
  
  CONCLUSIONS
  Patients with WD should be offered genetic counselling when considering pregnancy and offspring should always be screened for the disease. Diagnostic difficulties based on copper disturbances in asymptomatic children that are obligate carriers of the Wilson gene and the usefulness of molecular diagnosis are discussed.
authors.affiliation: Laboratoire de génétique moléculaire, pharmacogénétique, hormonologie, université Paris Sud, hôpital Bicêtre, AP-HP, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Dufernez
authors.forename: Alain
authors.initials: A
authors.lastname: Lachaux
authors.forename: Philippe
authors.initials: P
authors.lastname: Chappuis
authors.forename: Lionel
authors.initials: L
authors.lastname: De Lumley
authors.forename: Muriel
authors.initials: M
authors.lastname: Bost
authors.forename: France
authors.initials: F
authors.lastname: Woimant
authors.forename: Micheline
authors.initials: M
authors.lastname: Misrahi
authors.forename: Dominique
authors.initials: D
authors.lastname: Debray
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D027682:Cation Transport Proteins / Q000235:genetics; D002648:Child; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006239:Haplotypes; D006527:Hepatolenticular Degeneration / Q000175:diagnosis* / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases