Prevalence of UGT1A1 mutations in malay neonates with severe jaundice

Abstract

Aims Severe hyperbilirubinaemia is associated with permanent brain damage, also known as kernicterus. Many factors have been implicated in its development and more recently a genetic basis to many of these conditions has been established. We looked for the frequency of the UGT1A1 247 (T to C), A(TA) 7 TAA variant and G71R mutation in our Malay population. Methods Cord blood from 98 neonates without hyperbilirubinaemia (controls) was compared with cord blood from 125 neonates (cases) with severe hyperbilirbinaemia (total serum bilirubin >300 µmol/L). Samples were analysed for the nucleotide 247 polymorphism by Taqman single nucleotide polymorphism genotyping assay using Corbett Life Science Rotor-gene 6000 (Corbett Research, Australia) and the A(TA) 7 TAA variant by the Agilent 2100 bioanalyser. Results Of 246 neonates, no mutation for the UGT1A1 247 (T to C) was detected. However, four of 113 neonates with severe hyperbilirubinaemia (3.5%) were found to carry the A(TA) 7 mutation (heterozygous) and one of 87 controls (0.01%) carried the mutation (homozygous). The A(TA) 7 TAA variant was found to have a prevalence of 1.4% within the Malay population. Conclusion We have shown that neonatal jaundice may be contributed by a single dose of the A(TA) 7 TAA variant as an added risk factor to other factors that remain to be studied. We have also successfully established a rapid molecular technique that can be used for the screening of UGT1A1 mutations in neonatal jaundice.