Utilization of whole exome sequencing for undiagnosed diseases in Hong Kong

Abstract

Introduction: In the past few years, undiagnosed diseases programs worldwide have had increasing success in finding the etiology of pediatric diseases. However, in Hong Kong, whole exome sequencing (WES) is not funded by the government and there is yet to be a large collaborated effort to utilize this technology. We piloted the use of WES in pediatric patients supported by research funding and collaboration with overseas centers. Materials and Methods: 70 pediatric patients with undiagnosed diseases were recruited through the genetic clinic, and singleton DNA samples were sent for WES in collaboration with an overseas laboratory. After initial analysis of the variant based on the phenotype, segregation analysis for candidate pathogenic variants was performed locally. Results: Using a singleton WES strategy followed by targeted parental Sanger sequencing, pathogenic variants were found in over 30% (n=21) of the patients, including conditions recently identified with mutations identified in causative genes e.g. ASXL3, DDX3X, PIGO, PURA etc. We shall present some illustrative patients and address the challenges of implementing this technology in our local healthcare system. Conclusions: With limited resources, we piloted the application of WES for undiagnosed pediatric diseases in Hong Kong. Importantly our strategy of singleton WES followed by targeted parental Sanger sequencing has make it less costly compared to trio-based WES and yet achieving a diagnostic rate comparable to those reported overseas. Acknowledgement of grant support: This work was supported by grants from the S K Yee Medical Foundation and The Society for the Relief of Disabled Children.