@article {Bhatia31, author = {Neha S Bhatia and Jiin Ying Lim and Carine Bonnard and Jyn-Ling Kuan and Maggie Brett and Heming Wei and Breana Cham and Huilin Chin and Celia Bosso-Lefevre and Perumal Dharuman and Nathalie Escande-Beillard and Arun George Devasia and Chew Yin Jasmine Goh and Sylvia Kam and Wendy Kein-Meng Liew and Woei Kang Liew and Grace Lin and Kanika Jain and Alvin Yu-Jin Ng and Deepa Subramanian and Min Xie and Yuen-Ming Tan and Nilesh R Tawari and Zenia Tiang and Teck Wah Ting and Sumanty Tohari and Cheuk Ka Tong and Alexander Lezhava and Sarah B Ng and Hai Yang Law and Byrappa Venkatesh and Swati Tomar and Raman Sethi and Grace Tan and Arthi Shanmugasundaram and Denise Li-Meng Goh and Poh San Lai and Angeline Lai and Ee Shien Tan and Ivy Ng and Bruno Reversades and Ene Choo Tan and Roger Foo and Saumya Shekhar Jamuar}, editor = {, and , and Koh, Mark and Ho, Madeline and Wah, Lee Bee and Shek, Lynette and Tay, Stacey and Hui, Ng Kar and Ng, Pauline and Lim, Tony and Dunn, Ray and Connolly, John and Pouladi, Mahmoud and Tan, Patrick}, title = {Singapore Undiagnosed Disease Program: Genomic Analysis aids Diagnosis and Clinical Management}, volume = {106}, number = {1}, pages = {31--37}, year = {2021}, doi = {10.1136/archdischild-2020-319180}, publisher = {BMJ Publishing Group Ltd}, abstract = {Objective Use next-generation sequencing (NGS) technology to improve our diagnostic yield in patients with suspected genetic disorders in the Asian setting.Design A diagnostic study conducted between 2014 and 2019 (and ongoing) under the Singapore Undiagnosed Disease Program. Date of last analysis was 1 July 2019.Setting Inpatient and outpatient genetics service at two large academic centres in Singapore.Patients Inclusion criteria: patients suspected of genetic disorders, based on abnormal antenatal ultrasound, multiple congenital anomalies and developmental delay. Exclusion criteria: patients with known genetic disorders, either after clinical assessment or investigations (such as karyotype or chromosomal microarray).Interventions Use of NGS technology{\textemdash}whole exome sequencing (WES) or whole genome sequencing (WGS).Main outcome measures (1) Diagnostic yield by sequencing type, (2) diagnostic yield by phenotypical categories, (3) reduction in time to diagnosis and (4) change in clinical outcomes and management.Results We demonstrate a 37.8\% diagnostic yield for WES (n=172) and a 33.3\% yield for WGS (n=24). The yield was higher when sequencing was conducted on trios (40.2\%), as well as for certain phenotypes (neuromuscular, 54\%, and skeletal dysplasia, 50\%). In addition to aiding genetic counselling in 100\% of the families, a positive result led to a change in treatment in 27\% of patients.Conclusion Genomic sequencing is an effective method for diagnosing rare disease or previous {\textquoteleft}undiagnosed{\textquoteright} disease. The clinical utility of WES/WGS is seen in the shortened time to diagnosis and the discovery of novel variants. Additionally, reaching a diagnosis significantly impacts families and leads to alteration in management of these patients.}, issn = {0003-9888}, URL = {https://adc.bmj.com/content/106/1/31}, eprint = {https://adc.bmj.com/content/106/1/31.full.pdf}, journal = {Archives of Disease in Childhood} }