Abstract
Integration of genome sequencing in the diagnostic process for Thai infants with infantile cholestatic jaundice co-operated by Faculty of Medicine, Prince of Songkhla University and Health Systems Research Institute, Ministry of Public Health. To discover new genetic susceptibility of infantile cholestasis, next generation sequencing was implemented to operate in our study together with clinical finding and investigation. Focusing on biliary atresia, a half of cases had successful bile drainage from the hepatoportoenterostomy. According to similarity of clinical finding, the poor prognosis with naïve liver may be miss diagnosis from other cholestatic jaundice disease. Genetic biomarker became an important application to help discrimination of isolated biliary atresia and the others, improve post-operative outcome and delay queuing for liver transplantation. In our study, 64 individuals with cholestatic jaundice were included together with consent for blood sampling and genomic investigation under standard operation procedure of Genomic Thailand Consortium. All of retrieved samples and metadata information were processed at Translational Medicine Research Center (TMRC), Faculty of Medicine, Prince of Songkla University and delivered to Department of Medical Science, Ministry of Public Health. For the leftover specimens, whole exome sequencing was undergone to intensively discover pathogenic variants related to the cholestatic syndromes. Annotated exome sequences were comprehensively reviewed and discovered 45 possible deleterious variants. Moreover, genetic association was performed for SNPs located in ADD3 and EFEMP1 genes (rs2501577, rs17095355, rs6761893 and rs727878). The statistical appraisal of susceptibility shown significant association of first three SNPs with the disease together with additive biological interaction between both genes. In summary, we purpose that our study will be a beginning of implementation of high-throughput sequencing and genetic biomarker in pediatric surgical diseases.
