Abstract
Background :
Neonatal jaundice is common in South-East Asian and it is a potential cause of permanent brain damage. In most of the cases, no obvious aetiology is identified. Recently, mutations in the bilirubin uridine diphosphate glucuronosyl transferaselAl(UGTlAl) gene attributed to neonatal jaundice and hyperbilirubinemia syndromes have been reported in many populations. The underlying molecular defects are heterogeneous and may be attributed to any part of the five exons of the UGT1 gene.
Objective :
There were two main objectives in this study. The first objective of this study was to apply molecular techniques for the investigation of the UGT1A1 mutation in three babies [Bl, B2, B3] who presented with early onset of jaundice. Identifiable causes of pathological jaundice have been excluded earlier. An inherited phenomenon of this mutation will be demonstrated by doing family study and molecular analysis.
The second objective of the study was to develop a screening test for G71R mutation and to investigate the relationship of this mutation with neonatal hyperbilirubinemia.
Methodology :
For this purpose, sixty-eight Malay neonates were recruited. The subjects were divided into two groups:- hyperbilirubinemia and non-hyperbilirubinemia. Blood samples were taken and were screened for G71R mutation using denatured high performance liquid chromatography (DHPLC).
Results :
Nucleotides sequenced study of the three babies identified two different novel mutations within the studied gene in two Malay babies [Bl, B2]. One mutation was transversion G Æ C at nucleotide 1477 in exon 5 corresponding to G493R in Bl. Another mutation was transition AÆ G at nucleotide 964 in exon 2 corresponding to I322V in B2. A specific mutation i.e transition GÆA at nucleotide 211 in exon 1 corresponding to G71R was identified in B3, a Chinese. Previous studies have identified this specific mutation in Chinese, Korean and Japanese populations.
Population study for G71R mutation had revealed that it is present in four out of thirty-two hyperbilirubinemia neonates and one out of thirty-six non hyperbilirubinemia neonates with allele frequency of 0.03%. However, the association between the presence of this mutation and neonatal hyperbilirubinemia was insignificant (p> 0.05).
Conclusion :
Two novel intraexonic mutations were detected in two Malay babies [Bl, B2] and a specific G71R mutation was identified in a Chinese baby [B3}. These results suggest that mutations in UGT1A1 gene may play a role in the pathogenesis of early onset neonatal jaundice in Malay babies. Population study results showed that G71R mutation was found in Malay population; however its contribution to neonatal hyperbilirubinemia is equivocal due to limited samples sized and thus warrants further study in near future.
Dr. Narazah Mohd. Yusoff : (Supervisor)
Dr. Rosline Hassan : (Co-Supervisor)
Assoc. Prof. Dr. Amin Hans Van Rostenberghe : (Co-Supervisor)
