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

Arjan Pol, G. Herma Renkema, Albert Tangerman, Edwin G. Winkel, Udo F. Engelke, Arjan P.M. De Brouwer, Kevin C K Lloyd, Renee S. Araiza, Lambert Van Den Heuvel, Heymut Omran, Heike Olbrich, Marijn Oude Elberink, Christian Gilissen, Richard J. Rodenburg, Jörn Oliver Sass, K. Otfried Schwab, Hendrik Schäfer, Hanka Venselaar, J. Silvia Sequeira, Huub J.M. Op Den CampRon A. Wevers

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)120-129
Number of pages10
JournalNature Genetics
Volume50
Issue number1
DOIs
StatePublished - Jan 1 2018

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Selenium-Binding Proteins
Halitosis
Oxidoreductases
Mutation
Inborn Errors Metabolism
Lentivirus
Brassica
Dimethyl Sulfoxide
methylmercaptan
Knockout Mice
Formaldehyde
Fibroblasts
Bacteria

ASJC Scopus subject areas

  • Genetics

Cite this

Pol, A., Renkema, G. H., Tangerman, A., Winkel, E. G., Engelke, U. F., De Brouwer, A. P. M., ... Wevers, R. A. (2018). Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis. Nature Genetics, 50(1), 120-129. https://doi.org/10.1038/s41588-017-0006-7

Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis. / Pol, Arjan; Renkema, G. Herma; Tangerman, Albert; Winkel, Edwin G.; Engelke, Udo F.; De Brouwer, Arjan P.M.; Lloyd, Kevin C K; Araiza, Renee S.; Van Den Heuvel, Lambert; Omran, Heymut; Olbrich, Heike; Oude Elberink, Marijn; Gilissen, Christian; Rodenburg, Richard J.; Sass, Jörn Oliver; Schwab, K. Otfried; Schäfer, Hendrik; Venselaar, Hanka; Sequeira, J. Silvia; Op Den Camp, Huub J.M.; Wevers, Ron A.

In: Nature Genetics, Vol. 50, No. 1, 01.01.2018, p. 120-129.

Research output: Contribution to journalArticle

Pol, A, Renkema, GH, Tangerman, A, Winkel, EG, Engelke, UF, De Brouwer, APM, Lloyd, KCK, Araiza, RS, Van Den Heuvel, L, Omran, H, Olbrich, H, Oude Elberink, M, Gilissen, C, Rodenburg, RJ, Sass, JO, Schwab, KO, Schäfer, H, Venselaar, H, Sequeira, JS, Op Den Camp, HJM & Wevers, RA 2018, 'Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis', Nature Genetics, vol. 50, no. 1, pp. 120-129. https://doi.org/10.1038/s41588-017-0006-7
Pol A, Renkema GH, Tangerman A, Winkel EG, Engelke UF, De Brouwer APM et al. Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis. Nature Genetics. 2018 Jan 1;50(1):120-129. https://doi.org/10.1038/s41588-017-0006-7
Pol, Arjan ; Renkema, G. Herma ; Tangerman, Albert ; Winkel, Edwin G. ; Engelke, Udo F. ; De Brouwer, Arjan P.M. ; Lloyd, Kevin C K ; Araiza, Renee S. ; Van Den Heuvel, Lambert ; Omran, Heymut ; Olbrich, Heike ; Oude Elberink, Marijn ; Gilissen, Christian ; Rodenburg, Richard J. ; Sass, Jörn Oliver ; Schwab, K. Otfried ; Schäfer, Hendrik ; Venselaar, Hanka ; Sequeira, J. Silvia ; Op Den Camp, Huub J.M. ; Wevers, Ron A. / Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis. In: Nature Genetics. 2018 ; Vol. 50, No. 1. pp. 120-129.
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AU - Sass, Jörn Oliver

AU - Schwab, K. Otfried

AU - Schäfer, Hendrik

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