Publication: A novel 33-Gene targeted resequencing panel provides accurate, clinical-grade diagnosis and improves patient management for rare inherited anaemias
Issued Date
2016-10-01
Resource Type
ISSN
13652141
00071048
00071048
Other identifier(s)
2-s2.0-84978634344
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Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
British Journal of Haematology. Vol.175, No.2 (2016), 318-330
Suggested Citation
Noémi B.A. Roy, Edward A. Wilson, Shirley Henderson, Katherine Wray, Christian Babbs, Steven Okoli, Wale Atoyebi, Avery Mixon, Mary R. Cahill, Peter Carey, Jonathan Cullis, Julie Curtin, Helene Dreau, David J.P. Ferguson, Brenda Gibson, Georgina Hall, Joanne Mason, Mary Morgan, Melanie Proven, Amrana Qureshi, Joaquin Sanchez Garcia, Nongnuch Sirachainan, Juliana Teo, Ulf Tedgård, Doug Higgs, David Roberts, Irene Roberts, Anna Schuh A novel 33-Gene targeted resequencing panel provides accurate, clinical-grade diagnosis and improves patient management for rare inherited anaemias. British Journal of Haematology. Vol.175, No.2 (2016), 318-330. doi:10.1111/bjh.14221 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/41106
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Title
A novel 33-Gene targeted resequencing panel provides accurate, clinical-grade diagnosis and improves patient management for rare inherited anaemias
Author(s)
Noémi B.A. Roy
Edward A. Wilson
Shirley Henderson
Katherine Wray
Christian Babbs
Steven Okoli
Wale Atoyebi
Avery Mixon
Mary R. Cahill
Peter Carey
Jonathan Cullis
Julie Curtin
Helene Dreau
David J.P. Ferguson
Brenda Gibson
Georgina Hall
Joanne Mason
Mary Morgan
Melanie Proven
Amrana Qureshi
Joaquin Sanchez Garcia
Nongnuch Sirachainan
Juliana Teo
Ulf Tedgård
Doug Higgs
David Roberts
Irene Roberts
Anna Schuh
Edward A. Wilson
Shirley Henderson
Katherine Wray
Christian Babbs
Steven Okoli
Wale Atoyebi
Avery Mixon
Mary R. Cahill
Peter Carey
Jonathan Cullis
Julie Curtin
Helene Dreau
David J.P. Ferguson
Brenda Gibson
Georgina Hall
Joanne Mason
Mary Morgan
Melanie Proven
Amrana Qureshi
Joaquin Sanchez Garcia
Nongnuch Sirachainan
Juliana Teo
Ulf Tedgård
Doug Higgs
David Roberts
Irene Roberts
Anna Schuh
Other Contributor(s)
John Radcliffe Hospital
Churchill Hospital
Erlanger Hospital
Cork University Hospital
Royal Victoria Infirmary
Salisbury NHS Foundation Trust
Sydney Children's Hospitals Network
Nuffield Department of Clinical Medicine
Royal Hospital for Sick Children Glasgow
Southampton University Hospitals NHS Trust
Hospital Universitario Reina Sofia
Mahidol University
Skånes universitetssjukhus
Churchill Hospital
Erlanger Hospital
Cork University Hospital
Royal Victoria Infirmary
Salisbury NHS Foundation Trust
Sydney Children's Hospitals Network
Nuffield Department of Clinical Medicine
Royal Hospital for Sick Children Glasgow
Southampton University Hospitals NHS Trust
Hospital Universitario Reina Sofia
Mahidol University
Skånes universitetssjukhus
Abstract
© 2016 John Wiley & Sons Ltd Accurate diagnosis of rare inherited anaemias is challenging, requiring a series of complex and expensive laboratory tests. Targeted next-generation-sequencing (NGS) has been used to investigate these disorders, but the selection of genes on individual panels has been narrow and the validation strategies used have fallen short of the standards required for clinical use. Clinical-grade validation of negative results requires the test to distinguish between lack of adequate sequencing reads at the locations of known mutations and a real absence of mutations. To achieve a clinically-reliable diagnostic test and minimize false-negative results we developed an open-source tool (CoverMi) to accurately determine base-coverage and the ‘discoverability’ of known mutations for every sample. We validated our 33-gene panel using Sanger sequencing and microarray. Our panel demonstrated 100% specificity and 99·7% sensitivity. We then analysed 57 clinical samples: molecular diagnoses were made in 22/57 (38·6%), corresponding to 32 mutations of which 16 were new. In all cases, accurate molecular diagnosis had a positive impact on clinical management. Using a validated NGS-based platform for routine molecular diagnosis of previously undiagnosed congenital anaemias is feasible in a clinical diagnostic setting, improves precise diagnosis and enhances management and counselling of the patient and their family.