Universität zu Köln

Kaczmarek, Alexander Tobias, Bahlmann, Nike, Thaqi, Besarta, May, Patrick ORCID: 0000-0001-8698-3770 and Schwarz, Guenter ORCID: 0000-0002-2118-9338 (2021). Machine learning-based identification and characterization of 15 novel pathogenic SUOX missense mutations. Mol. Genet. Metab., 134 (1-2). S. 188 - 195. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1096-7206

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Abstract

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 as-sociated 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 aware-ness 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-equilib-rium and the combination of our results with published SO missense and protein truncating variants, we calcu-lated 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. (c) 2021 Published by Elsevier Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kaczmarek, Alexander Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Bahlmann, Nike UNSPECIFIED UNSPECIFIED UNSPECIFIED Thaqi, Besarta UNSPECIFIED UNSPECIFIED UNSPECIFIED May, Patrick UNSPECIFIED orcid.org/0000-0001-8698-3770 UNSPECIFIED Schwarz, Guenter UNSPECIFIED orcid.org/0000-0002-2118-9338 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-572485
DOI:	10.1016/j.ymgme.2021.07.011
Journal or Publication Title:	Mol. Genet. Metab.
Volume:	134
Number:	1-2
Page Range:	S. 188 - 195
Date:	2021
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1096-7206
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SULFITE OXIDASE DEFICIENCY; MECHANISM; EXPRESSION; DATABASE; DBNSFP Multiple languages Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57248