Journal Article

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

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

2018

Overview

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 H 2 O 2 , formaldehyde, and H 2 S, 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. Ron Wevers and colleagues report that mutations in the methanethiol oxidase gene SELENBP1 cause chronic extraoral halitosis. They find that enzyme deficiency leads to increased levels of methanethiol and dimethylsulfide in the breath and that knockout mice have similar biochemical phenotypes.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/308/2056 / 692/699/317 / Agriculture / Animal Genetics and Genomics / Animals / Bacteria / Biochemical characteristics / Biochemistry / Biomedical and Life Sciences / Biomedicine / Breath Tests / Cancer Research / Cell Line / Cells, Cultured / Chromatography / Dimethyl sulfide / Dimethyl Sulfoxide - blood / Dimethyl Sulfoxide - cerebrospinal fluid / Dimethyl Sulfoxide - urine / Enzymatic activity / Excretion / Families & family life / Fibroblasts / Fluids / Gases / Gene Function / Halitosis - enzymology / Halitosis - genetics / Human Genetics / Humans / Hydrogen / Hydrogen peroxide / Hydrogen sulfide / Inborn errors of metabolism / Liver cancer / Metabolism / Methanethiol / Methanethiol oxidase / Methylotrophic bacteria / Mice, Inbred C57BL / Mice, Knockout / Mutation / Odor / Off odor / Oxidase / Oxidoreductases - genetics / Patients / Proteins / Selenium / Selenium-Binding Proteins - deficiency / Selenium-Binding Proteins - genetics / Selenium-Binding Proteins - metabolism / Spectrum analysis / Sulfur / Tumors / Urine