Standardized practices for RNA diagnostics using clinically accessible specimens reclassifies 75% of putative splicing variants

AM Bournazos; LG Riley; S Bommireddipalli; L Ades; LS Akesson; M Al-Shinnag; SI Alexander; AD Archibald; S Balasubramaniam; Y Berman; V Beshay; K Boggs; J Bojadzieva; NJ Brown; SJ Bryen; MF Buckley; B Chong; MR Davis; R Dawes; M Delatycki; L Donaldson; L Downie; C Edwards; M Edwards; A Engel; LJ Ewans; F Faiz; A Fennell; M Field; ML Freckmann; L Gallacher; R Gear; H Goel; S Goh; L Goodwin; B Hanna; J Harraway; M Higgins; G Ho; BK Hopper; AE Horton; MF Hunter; AJ Huq; S Josephi-Taylor; H Joshi; E Kirk; E Krzesinski; KR Kumar; F Lemckert; RJ Leventer; SE Lindsey-Temple; S Lunke; A Ma; S Macaskill; A Mallawaarachchi; M Marty; JE Marum; HJ McCarthy; MP Menezes; A McLean; D Milnes; S Mohammad; D Mowat; A Niaz; EE Palmer; C Patel; SG Patel; D Phelan; JR Pinner; S Rajagopalan; M Regan; J Rodgers; M Rodrigues; RH Roxburgh; R Sachdev; T Roscioli; R Samarasekera; SA Sandaradura; E Savva; T Schindler; M Shah; IB Sinnerbrink; JM Smith; RJ Smith; A Springer; Z Stark; SP Strom; CM Sue; K Tan; TY Tan; E Tantsis; MC Tchan; BA Thompson; AH Trainer; K van Spaendonck-Zwarts; R Walsh; L Warwick; S White; SM White; MG Williams

Journal article

Standardized practices for RNA diagnostics using clinically accessible specimens reclassifies 75% of putative splicing variants

AM Bournazos, LG Riley, S Bommireddipalli, L Ades, LS Akesson, M Al-Shinnag, SI Alexander, AD Archibald, S Balasubramaniam, Y Berman, V Beshay, K Boggs, J Bojadzieva, NJ Brown, SJ Bryen, MF Buckley, B Chong, MR Davis, R Dawes, M Delatycki Show all

Genetics in Medicine | Published : 2022

DOI: 10.1016/j.gim.2021.09.001

Abstract

Purpose: Genetic variants causing aberrant premessenger RNA splicing are increasingly being recognized as causal variants in genetic disorders. In this study, we devise standardized practices for polymerase chain reaction (PCR)-based RNA diagnostics using clinically accessible specimens (blood, fibroblasts, urothelia, biopsy). Methods: A total of 74 families with diverse monogenic conditions (31% prenatal-congenital onset, 47% early childhood, and 22% teenage-adult onset) were triaged into PCR-based RNA testing, with comparative RNA sequencing for 19 cases. Results: Informative RNA assay data were obtained for 96% of cases, enabling variant reclassification for 75% variants that can be used ..

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University of Melbourne Researchers

Alison Archibald Author

Martin Delatycki Author

Lilian Downie Author

Rick Leventer Author

Grants

Awarded by University of Sydney

Funding Acknowledgements

Sandra T. Cooper is supported by a National Health and Medical Research Council of Australia Senior Research Fellowship under grant APP1136197. This project received funding through the Medical Research Future Fund Rapid Applied Research Translation Program grant awarded to Sydney Health Partners. Adam M. Bournazos is supported by a University of Sydney Research Training Scholarship. Part of this work was supported by Luminesce Alliance--Innovation for Children's Health, a not for profit cooperative joint venture between the Sydney Children's Hospitals Network, the Children's Medical Research Institute, and the Children's Cancer Institute. It has been established with the support of the New South Wales Government to coordinate and integrate pediatric research. Luminesce Alliance is also affiliated with the University of Sydney and the University of New South Wales, Sydney. Carolyn M. Sue is a National Health and Medical Research Council Practitioner Fellow under APP1136800.