Singapore Undiagnosed Disease Program: Genomic Analysis aids Diagnosis and Clinical Management.

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-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 '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.

journal_name

Arch Dis Child

authors

Bhatia NS,Lim JY,Bonnard C,Kuan JL,Brett M,Wei H,Cham B,Chin H,Bosso-Lefevre C,Dharuman P,Escande-Beillard N,Devasia AG,Goh CYJ,Kam S,Liew WK,Liew WK,Lin G,Jain K,Ng AY,Subramanian D,Xie M,Tan YM,Tawari NR,T

doi

10.1136/archdischild-2020-319180

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

31-37

issue

1

eissn

0003-9888

issn

1468-2044

pii

archdischild-2020-319180

journal_volume

106

pub_type

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