Mutations in SELENBP1 encoding a novel humanmethanethiol oxidase cause extra-oral halitosis

摘要

Selenium binding protein1 (SELENBP1) has been associated with several cancers. Its exact role was unknown. We show that SELENBP1 is a methanethiol oxidase (MTO), related to MTO of methylotrophic bacteria, converting methanethiol to H2O2, formaldehyde and H2S, an activity not known to exist in humans. Mutations in SELENBP1 were found in five patients with a cabbage-like smelling breath. Increased levels of methanethiol and dimethylsulfide are the main odorous compounds in their breath and responsible for the malodor. Increased urinary excretion of dimethylsulfoxide is a diagnostic biomarker of MTO-deficiency. Patient fibroblasts showed reduced amounts of SELENBP1 protein and deficient MTO enzymatic activity which could be restored by lentiviral-mediated expression of the wild-type SELENBP1 gene. A knockout mouse line showed the same biochemical characteristics. Our data define a novel inborn error of metabolism caused by MTO-deficiency leading to a malodor syndrome. MTO deficiency may be a frequent inborn error of metabolism.