title: Inheritance of hyperbilirubinemia: evidence for a major autosomal recessive gene.
abstract: OBJECTIVE
  To clarify the precise mode of inheritance of Gilbert syndrome, an unconjugated familial hyperbilirubinemia, where impaired bilirubin conjugation is caused by reduced UGT1A1 activity determined by a defective function of the A(TA)6TAA promoter region of the UGT1A1 gene.
  
  
  METHODS
  Serum bilirubin levels were measured in a large, homogeneous resident population from North-Eastern Italy, consisting of 1.639 males (age 44.5+/-13.9, range 18-89 years), and 1.420 females (age 45.1+/-15.0, range 18-85). In 112 nuclear families from hyperbilirubinemic probands living in the same area a complex segregation analysis was then performed. In both samples we carefully excluded potentially confounding factors of bilirubin levels (alcohol abuse, excessive cigarette smoking, drug consumption, overt haemolysis and liver disease).
  
  
  RESULTS
  Mean serum bilirubin concentrations are higher in males than in females, showing fluctuations through the different age periods in males. Complex segregation results demonstrate that unconjugated hyperbilirubinemia exhibits a precise mode of inheritance in which a major recessive gene with a frequency of 0.45 is responsible for higher serum bilirubin values.
  
  
  CONCLUSIONS
  This major recessive gene accounts only for a part of the serum bilirubin concentration, thus implying additional, environmental factors for the clinical appearance of GS.
authors.affiliation: Clinical Genetics and Epidemiology, Department of Pediatrics, University of Padua, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Clementi
authors.forename: E
authors.initials: E
authors.lastname: Di Gianantonio
authors.forename: L
authors.initials: L
authors.lastname: Fabris
authors.forename: P
authors.initials: P
authors.lastname: Forabosco
authors.forename: M
authors.initials: M
authors.lastname: Strazzabosco
authors.forename: R
authors.initials: R
authors.lastname: Tenconi
authors.forename: L
authors.initials: L
authors.lastname: Okolicsanyi
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001663:Bilirubin / Q000097:blood*; D005260:Female; D005878:Gilbert Disease / Q000097:blood / Q000235:genetics*; D006801:Humans; D007558:Italy; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010375:Pedigree; D012494:Sampling Studies; D017678:Sex Distribution
chemical_list: D001663:Bilirubin