Molecular diagnosis of heritable unconjugated hyperbilirubinemias
Mammaev, S.N.
Klinicheskaia Laboratornaia Diagnostika 12: 8-13
2005
ISSN/ISBN: 0869-2084 PMID: 16498946 Document Number: 588084
There is considerable evidence suggesting that genetic damages to human uridine diphosphate glucuronyltransferase (UDPGT) gene located on clhromosome 2q37 are responsible for hereditary unconjugated hyperbilirubinemias (HUHB). The Crigler-Najjar syndrome of types I and II is characterized by structural mutations on one of 5 exons of HUHB gene, resulting in the synthesis of defective catalytically inactive isoforms of the enzyme. In Gilbert's syndrome, genetic alterations are located at the promoter of the gene and accompanied by the nucleotide insert of thymine adenine (TA). Promoter prolongation impairs the binding of IID transcription factor and leads to the decreased production of the enzyme UDPGT 1,1. Examination of the molecular epidemiology of gene mutations of UDPGT 1,1 that is typical of Gilbert's syndrome ascertained a great difference in the indices, from 2 to 16% in the Asian and European populations, respectively. In addition to polymerase chain reaction, high performance liquid chromatography may be used for the diagnosis of genetic alterations in Gilbert's syndrome.