Reference : Machine learning-based identification and characterization of 15 novel pathogenic SUO...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Life sciences : Genetics & genetic processes
Systems Biomedicine
http://hdl.handle.net/10993/47808
Machine learning-based identification and characterization of 15 novel pathogenic SUOX missense mutations
English
Kaczmarek, Alexander Tobias [> >]
Bahlmann, Nike [> >]
Thaqi, Besarta [> >]
May, Patrick mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core]
Schwarz, Guenter [> >]
8-Aug-2021
Molecular Genetics and Metabolism
Yes (verified by ORBilu)
International
1096-7192
[en] Isolated sulfite oxidase deficiency ; Molybdenum cofactor ; Machine learning ; Random forest classification ; Sulfite oxidase ; SUOX
[en] Isolated sulfite oxidase deficiency (ISOD) is a rare hereditary metabolic disease caused by absence of functional sulfite oxidase (SO) due to mutations of the SUOX gene. SO oxidizes toxic sulfite and sulfite accumulation is associated with neurological disorders, progressive brain atrophy and early death. Similarities of these neurological symptoms to abundant diseases like neonatal encephalopathy underlines the raising need to increase the awareness for ISOD. Here we report an interdisciplinary approach utilizing exome/genome data derived from gnomAD database as well as published variants to predict the pathogenic outcome of 303 naturally occurring SO missense variants and combining these with activity determination. We identified 15 novel ISOD-causing SO variants and generated a databank of pathogenic SO missense variants to support future diagnosis of ISOD patients. We found six inactive variants (W101G, H118Y, E197K, R217W, S427W, D512Y, Q518R) and seven (D110H, P119S, G121E, G130R, Y140C, R269H, Q396P, R459Q) with severe reduction in activity. Based on the Hardy-Weinberg-equilibrium and the combination of our results with published SO missense and protein truncating variants, we calculated the first comprehensive incidence rate for ISOD of 1 in 1,377,341 births and provide a pathogenicity score to 303 naturally occurring SO missense variants.
Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
National Centre for Excellence Missing in Research on Parkinson‟s disease (NCER-PD), BMBF Treat-ION grant (01GM1907).
Researchers
http://hdl.handle.net/10993/47808
10.1016/j.ymgme.2021.07.011
https://www.sciencedirect.com/science/article/pii/S1096719221007617
FnR ; FNR11583046 > Roland Krause > MechEPI > Epileptogenesis Of Genetic Epilepsies > 01/04/2018 > 30/06/2021 > 2017

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Limited access
1-s2.0-S1096719221007617-main.pdfAuthor postprint1.47 MBRequest a copy

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.