1. Singapore Undiagnosed Disease Program: Genomic Analysis aids Diagnosis and Clinical Management
- Author
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Breana Cham, Jiin Ying Lim, Wendy K.M. Liew, Yuen-Ming Tan, Jyn-Ling Kuan, Bruno Reversades, Raman Sethi, Alvin Yu Jin Ng, Nathalie Escande-Beillard, Alexander Lezhava, Sumanty Tohari, Heming Wei, Arun George Devasia, Deepa Subramanian, Sylvia Kam, Woei Kang Liew, Min Xie, Kanika Jain, Saumya Shekhar Jamuar, Hai-Yang Law, Ee Shien Tan, Nilesh R. Tawari, Swati Tomar, Ene-Choo Tan, Ivy Ng, Carine Bonnard, Grace Lin, Angeline Lai, Chew Yin Jasmine Goh, Perumal Dharuman, Poh San Lai, Arthi Shanmugasundaram, Huilin Chin, Neha Singh Bhatia, Denise L.M. Goh, Maggie Brett, Célia Bosso-Lefèvre, Grace K. Tan, Teck Wah Ting, Roger Foo, Sarah B Ng, Cheuk Ka Tong, Byrappa Venkatesh, and Zenia Tiang
- Subjects
Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Developmental Disabilities ,Genetic counseling ,Psychological intervention ,Disease ,Undiagnosed Diseases ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Abnormalities, Multiple ,Child ,Exome sequencing ,030304 developmental biology ,Whole genome sequencing ,Singapore ,0303 health sciences ,business.industry ,High-Throughput Nucleotide Sequencing ,Infant ,medicine.disease ,Dysplasia ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,business ,030217 neurology & neurosurgery ,AIDS diagnosis ,Rare disease - Abstract
ObjectiveUse next-generation sequencing (NGS) technology to improve our diagnostic yield in patients with suspected genetic disorders in the Asian setting.DesignA diagnostic study conducted between 2014 and 2019 (and ongoing) under the Singapore Undiagnosed Disease Program. Date of last analysis was 1 July 2019.SettingInpatient and outpatient genetics service at two large academic centres in Singapore.PatientsInclusion 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).InterventionsUse of NGS technology—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.ResultsWe 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.ConclusionGenomic sequencing is an effective method for diagnosing rare disease or previous ‘undiagnosed’ 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.
- Published
- 2020
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