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Nat Genet. 2018 Jan;50(1):120-129. doi: 10.1038/s41588-017-0006-7. Epub 2017 Dec 18.

Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis.

Author information

1
Department of Microbiology, IWWR, Faculty of Science, Radboud University, Nijmegen, The Netherlands.
2
Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands.
3
Department of Internal Medicine, RUNMC, Nijmegen, The Netherlands.
4
Center for Dentistry and Oral Hygiene, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
5
Clinic for Periodontology, Amsterdam, The Netherlands.
6
Department of Human Genetics, RUNMC, Nijmegen, The Netherlands.
7
Department of Surgery, School of Medicine, and Mouse Biology Program, University of California, Davis, Davis, CA, USA.
8
Mouse Biology Program, University of California, Davis, Davis, CA, USA.
9
Department of Pediatrics, RUNMC, Nijmegen, The Netherlands.
10
Klinik für Kinder und Jugendmedizin, Universitätsklinikum Münster, Münster, Germany.
11
Bioanalytics and Biochemistry, Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, Rheinbach, Germany.
12
Department of Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg, Germany.
13
School of Life Sciences, University of Warwick, Coventry, UK.
14
Centre for Molecular and Biomolecular Informatics, RUNMC, Nijmegen, The Netherlands.
15
Metabolic Unit-Pediatric Department, Hospital de Dona Estefânia, CHLC, Lisbon, Portugal.
16
Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands. ron.wevers@radboudumc.nl.

Abstract

Selenium-binding protein 1 (SELENBP1) has been associated with several cancers, although its exact role is unknown. We show that SELENBP1 is a methanethiol oxidase (MTO), related to the MTO in methylotrophic bacteria, that converts methanethiol to H2O2, formaldehyde, and H2S, an activity not previously known to exist in humans. We identified mutations in SELENBP1 in five patients with cabbage-like breath odor. The malodor was attributable to high levels of methanethiol and dimethylsulfide, the main odorous compounds in their breath. Elevated urinary excretion of dimethylsulfoxide was associated with MTO deficiency. Patient fibroblasts had low SELENBP1 protein levels and were deficient in MTO enzymatic activity; these effects were reversed by lentivirus-mediated expression of wild-type SELENBP1. Selenbp1-knockout mice showed biochemical characteristics similar to those in humans. Our data reveal a potentially frequent inborn error of metabolism that results from MTO deficiency and leads to a malodor syndrome.

PMID:
29255262
PMCID:
PMC5742538
DOI:
10.1038/s41588-017-0006-7
[Indexed for MEDLINE]
Free PMC Article

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