{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:46:31Z","timestamp":1793213191947,"version":"4.5.0"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T00:00:00Z","timestamp":1664064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001348","name":"Agency for Science, Technology and Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["CSAINV21jun\u20100003"],"award-info":[{"award-number":["CSAINV21jun\u20100003"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Children with genetic diseases endure a prolonged and costly \u201cdiagnostic odyssey.\u201d The use of whole exome sequencing (WES) and whole genome sequencing (WGS) has improved the diagnosis rate, ending the odyssey. However, the additional\u00a0costs associated WES\/WGS has impeded their adoption in Asian settings. We aim to estimate the expected change to the mean number of diagnostic tests used, and the associated costs from a decision to use WES early in the diagnostic pathways of pediatric phenotypes, as compared to Existing Practice. Retrospective data from a patient cohort recruited under the Singapore Undiagnosed Disease Program from a tertiary hospital in Singapore, for the period October 2004 to September 2020, was analyzed. Four phenotype\u2010specific subgroups were used: multiple congenital anomalies (MCA) without developmental delay; global developmental delay (GDD); neuromuscular disorder (NMD) and primary immunodeficiency disorder (PID). Patients had undergone a traditional diagnostic pathway and received a diagnosis either through clinical exome or WES or WGS. A costs only analysis was performed, by tabulating the outcomes \u201ctest quantity\u201d and \u201ctest costs\u201d incurred by patients. The outcomes were compared with alternate diagnostic pathways which incorporates the early introduction of WES trio testing. To include uncertainty in cost outcomes, simulation studies were done on uncertain parameters. Cost outcomes are reported in Singapore dollars (S$). The 92 included patients had MCA (<jats:italic>n<\/jats:italic>\u00a0=\u00a048), GDD (<jats:italic>n<\/jats:italic>\u00a0=\u00a029), NMD (<jats:italic>n<\/jats:italic>\u00a0=\u00a010), or PID (<jats:italic>n<\/jats:italic>\u00a0=\u00a05). Patients were aged between 18\u2009days and 26\u2009years, 52.2% were males. The majority were of Chinese ethnicity (81.5%). If patients had access to WES directly, test quantity reduced by 97.38% for MCA, 96.98% for GDD, 96.56% for NMD, and 99.84% for PID. The expected cost savings per patient were $5940 for MCA (US$4433), $5342 for GDD (US$3986), $4622 for NMD (US$3449), and $58,497 for PID (US$43,654). Uncertainty assessment for MCA and GDD patients showed a respective likelihood of 86.9% and 97.4% for cost savings. Adoption of alternate diagnostic pathways with early WES in selected pediatric subgroups are likelt to reduce costs, when compared to Existing Practice. Benefits arising from earlier diagnosis, and the potential cost savings could mitigate the large initial cost of implementing WES in Asian settings.<\/jats:p>","DOI":"10.1002\/ajmg.a.62974","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T05:39:15Z","timestamp":1664170755000},"page":"3482-3491","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Reduced resource utilization with early use of next\u2010generation sequencing in rare genetic diseases in an Asian cohort"],"prefix":"10.1002","volume":"188","author":[{"given":"Nuraini","family":"Nazeha","sequence":"first","affiliation":[{"name":"Health Services and Systems Research Duke\u2010NUS Medical School  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4514-6869","authenticated-orcid":false,"given":"Ai Ling","family":"Koh","sequence":"additional","affiliation":[{"name":"Genetics Service, Department of Paediatrics KK Women's and Children's Hospital  Singapore Singapore"},{"name":"SingHealth Duke\u2010NUS Genomic Medicine Centre  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Kam","sequence":"additional","affiliation":[{"name":"Genetics Service, Department of Paediatrics KK Women's and Children's Hospital  Singapore Singapore"},{"name":"SingHealth Duke\u2010NUS Genomic Medicine Centre  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiin Ying","family":"Lim","sequence":"additional","affiliation":[{"name":"Genetics Service, Department of Paediatrics KK Women's and Children's Hospital  Singapore Singapore"},{"name":"SingHealth Duke\u2010NUS Genomic Medicine Centre  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise Li Meng","family":"Goh","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"},{"name":"Department of Paediatrics, Khoo Teck Puat \u2010 National University Children's Medical Institute National University Hospital  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2341-8349","authenticated-orcid":false,"given":"Saumya Shekhar","family":"Jamuar","sequence":"additional","affiliation":[{"name":"Genetics Service, Department of Paediatrics KK Women's and Children's Hospital  Singapore Singapore"},{"name":"SingHealth Duke\u2010NUS Genomic Medicine Centre  Singapore Singapore"},{"name":"SingHealth Duke\u2010NUS Institute of Precision Medicine  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Graves","sequence":"additional","affiliation":[{"name":"Health Services and Systems Research Duke\u2010NUS Medical School  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,25]]},"reference":[{"key":"e_1_2_13_2_1","first-page":"1","article-title":"Approach to patients with neuromuscular disorders","author":"Amato A. 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