https://scholars.lib.ntu.edu.tw/handle/123456789/525090
Title: | Exome sequencing for paediatric-onset diseases: impact of the extensive involvement of medical geneticists in the diagnostic odyssey | Authors: | Mak C.C. Leung G.K. Mok G.T. Yeung K.S. Yang W. Fung C.-W. Chan S.H. Lee S.-L. NI-CHUNG LEE Pfundt R. Lau Y.-L. Chung B.H. |
Issue Date: | 2018 | Publisher: | Nature Publishing Group | Journal Volume: | 3 | Journal Issue: | 1 | Start page/Pages: | 19 | Source: | npj Genomic Medicine | Abstract: | Currently, offering whole-exome sequencing (WES) via collaboration with an external laboratory is increasingly common. However, the receipt of a WES report can be merely the beginning of a continuing exploration process rather than the end of the diagnostic odyssey. The laboratory often does not have the information the physician has, and any discrepancies in variant interpretation must be addressed by a medical geneticist. In this study, we performed diagnostic WES of 104 patients with paediatric-onset genetic diseases. The post-exome review of WES reports by the clinical geneticist led to a more comprehensive assessment of variant pathogenicity in 16 cases. The overall diagnostic yield was 41% (n = 43). Among these 43 diagnoses, 51% (22/43) of the pathogenic variants were nucleotide changes that have not been previously reported. The time required for the post-exome review of the WES reports varied, and 26% (n = 27) of the reports required an extensive amount of time (>3 h) for the geneticist to review. In this predominantly Chinese cohort, we highlight the importance of discrepancies between global and ethnic-specific frequencies of a genetic variant that complicate variant interpretation and the significance of post-exome diagnostic modalities in genetic diagnosis using WES. The challenges faced by geneticists in interpreting WES reports are also discussed. ? 2018, The Author(s). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85051223146&doi=10.1038%2fs41525-018-0056-5&partnerID=40&md5=4677f5e135a1dc6cd53e1c789f642f3e https://scholars.lib.ntu.edu.tw/handle/123456789/525090 |
ISSN: | 2056-7944 | DOI: | 10.1038/s41525-018-0056-5 | SDG/Keyword: | adolescent; adult; Article; child; childhood disease; Chinese; clinical outcome; cohort analysis; cord blood stem cell transplantation; diagnostic value; ethnicity; exome; female; gene; gene frequency; generalized dystonia; genetic disorder; genetic variability; gjb2 gene; human; infant; kmt2b gene; Lenz Majewski hyperostotic dwarfism; lifestyle modification; major clinical study; male; medical geneticist; muscular dystrophy; pancreas disease; parkinsonism; pathogenicity; patient referral; phenotype; priority journal; Sanger sequencing; Shwachman Bodian Diamond syndrome; squamous cell carcinoma; whole exome sequencing |
Appears in Collections: | 醫學系 |
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