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.

CASE REPORT:

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.

CONCLUSION:

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: Yoshihiro Maruo, Mahdiyeh Behnam, Shinichi Ikushiro, Sayuri Nakahara, Narges Nouri, Mansour Salehi
• Journal: Journal of gastrointestinal and liver diseases : JGLD (J Gastrointestin Liver Dis) Vol. 24 Issue 4 Pg. 523-6 (Dec 2015) ISSN: 1842-1121 [Electronic] Romania
• PMID: 26697581 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• UGT1A1 enzyme
• Glucuronosyltransferase
• Bilirubin

Topics

• Animals
• Bilirubin (blood)
• Biomarkers (blood)
• COS Cells
• Child, Preschool
• Chlorocebus aethiops
• Crigler-Najjar Syndrome (diagnosis, enzymology, genetics, therapy)
• DNA Mutational Analysis
• Fatal Outcome
• Female
• Genetic Predisposition to Disease
• Glucuronosyltransferase (genetics, metabolism)
• Heredity
• Humans
• Infant, Newborn
• Iran
• Liver Transplantation
• Male
• Mutation
• Phenotype
• Transfection
• Treatment Outcome