title: Two Different UGT1A1 Mutations causing Crigler-Najjar Syndrome types I and II in an Iranian Family.
abstract: BACKGROUND
  Crigler-Najjar syndrome type I (CN-1) and type II (CN-2) are rare hereditary unconjugated hyperbilirubinemia disorders. However, there have been no reports regarding the co-existence of CN-1 and CN-2 in one family. We experienced a case of an Iranian family that included members with either CN-1 or CN-2. Genetic analysis revealed a mutation in the bilirubin UDP-glucuronosyltransferase (UGT1A1) gene that resulted in residual enzymatic activity.
  
  
  METHODS
  The female proband developed severe hyperbilirubinemia [total serum bilirubin concentration (TB) = 34.8 mg/dL] with bilirubin encephalopathy (kernicterus) and died after liver transplantation. Her family history included a cousin with kernicterus (TB = 30.0 mg/dL) diagnosed as CN-1. Her great grandfather (TB unknown) and uncle (TB = 23.0 mg/dL) developed jaundice, but without any treatment, they remained healthy as CN-2.
  
  
  RESULTS
  The affected cousin was homozygous for a novel frameshift mutation (c.381insGG, p.C127WfsX23). The affected uncle was compound heterozygous for p.C127WfsX23 and p.V225G linked with A(TA)7TAA. p.V225G-UGT1A1 reduced glucuronidation activity to 60% of wild-type. Thus, linkage of A(TA)7TAA and p.V225G might reduce UGT1A1 activity to 18%-36 % of the wild-type.
  
  
  CONCLUSIONS
  Genetic and in vitro expression analyses are useful for accurate genetic counseling for a family with a history of both CN-1 and CN-2.
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Otsu, Shiga, Japan. maruo@belle.shiga-med.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Maruo
authors.affiliation: Medical Genetics Laboratory of Genome, Isfahan, Iran.
authors.forename: Mahdiyeh
authors.initials: M
authors.lastname: Behnam
authors.affiliation: Department of Biotechnology, Toyama Prefectural University, Imizu, Toyama, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ikushiro
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Nakahara
authors.affiliation: Labkhand Clinic, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Narges
authors.initials: N
authors.lastname: Nouri
authors.affiliation: Division of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mansour
authors.initials: M
authors.lastname: Salehi
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D019556:COS Cells; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D003414:Crigler-Najjar Syndrome / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000628:therapy; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D005260:Female; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D040941:Heredity; D006801:Humans; D007231:Infant, Newborn; D007492:Iran; D016031:Liver Transplantation; D008297:Male; D009154:Mutation; D010641:Phenotype; D014162:Transfection; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D015415:Biomarkers; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme