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

Article

ISSN

13652141
00071048

DOI

10.1111/bjh.14221

Other identifier(s)

2-s2.0-84978634344

Rights

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

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

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.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/123456789/41106

Collections

Scopus 2016-2017