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Monoamine oxidase A activity in fibroblasts as a functional confirmation of MAOA variants

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dc.contributor Landspitali - The National University Hospital of Iceland
dc.contributor.author Peters, Tessa M.A.
dc.contributor.author Lammerts van Bueren, Irma
dc.contributor.author Geurtz, Ben P.B.H.
dc.contributor.author Coene, Karlien L.M.
dc.contributor.author de Leeuw, Nicole
dc.contributor.author Brunner, Han G.
dc.contributor.author Jónsson, Jón Jóhannes
dc.contributor.author Willemsen, Michèl A.A.P.
dc.contributor.author Wevers, Ron A.
dc.contributor.author Verbeek, Marcel M.
dc.date.accessioned 2022-06-10T01:03:19Z
dc.date.available 2022-06-10T01:03:19Z
dc.date.issued 2020-12-28
dc.identifier.citation Peters , T M A , Lammerts van Bueren , I , Geurtz , B P B H , Coene , K L M , de Leeuw , N , Brunner , H G , Jónsson , J J , Willemsen , M A A P , Wevers , R A & Verbeek , M M 2020 , ' Monoamine oxidase A activity in fibroblasts as a functional confirmation of MAOA variants ' , JIMD Reports , vol. 58 , no. 1 , pp. 114-121 . https://doi.org/10.1002/jmd2.12194
dc.identifier.issn 2192-8304
dc.identifier.other PURE: 42949155
dc.identifier.other PURE UUID: 82365308-c6af-494c-b5fd-d94d01a03000
dc.identifier.other Scopus: 85102315724
dc.identifier.other unpaywall: 10.1002/jmd2.12194
dc.identifier.uri https://hdl.handle.net/20.500.11815/3230
dc.description The authors would like to thank Frans van den Brandt, Saskia van der Velde-Visser, and Marlie H. M. Jacobs-Camps for their work in culturing the fibroblasts and Astrid van Rens for performing the protein assay. Furthermore, the authors thank Stichting Stofwisselkracht and for their financial support for this study. The study was funded by Stofwisselkracht under the project name of “Innovative diagnostics in cerebrospinal fluid of patients with neurometabolic disorders” (KLM Coene and MM Verbeek). The authors confirm independence from the sponsor; the content of the article has not been influenced by the sponsor. Lastly, the authors thank the The Society for the Study of Inborn Errors of Metabolism for covering the article processing charge.
dc.description.abstract Monoamine oxidase A (MAO‐A) deficiency is a rare inborn error of metabolism with impaired degradation of biogenic amines including 5‐hydroxytryptamine (5‐HT), resulting in borderline intellectual disability and behavioral abnormalities. Genetic variants in MAOA need functional confirmation to enable a definite diagnosis. To this end, we developed an inexpensive, simple and nonradioactive MAO‐A activity assay based on the conversion of 5‐HT into 5‐hydroxyindoleacetic acid (5‐HIAA). Fibroblast cell lysates were incubated with 5‐HT and aldehyde dehydrogenase to allow 5‐HIAA production. 5‐HIAA was quantified using high‐performance liquid chromatography with fluorimetric detection. We optimized reaction mixture components, pH, and substrate concentration and tested linearity and specificity of the assay. We verified the functional validity of the enzyme assay using fibroblasts of controls, female mutation carriers and MAO‐A deficient patients. This included a newly described patient with a novel MAOA variant (c.1336G>A, p.(Glu446Lys)), who represents the fifth MAO‐A deficiency family so far. The optimized enzyme assay showed good linearity and specificity. Application to clinical samples showed a 100% differentiation of affected patients (with negligible MAO‐A enzyme activity) and controls or mutation carriers. In conclusion, the described MAO‐A activity assay is easy to implement and can readily be used to test the pathogenicity of variants in the MAOA gene in a clinical setting. Especially in this era of whole‐exome (and whole‐genome) sequencing, this functional assay fulfills a clinical need for functional confirmation of a suspected diagnosis of MAO‐A deficiency.
dc.format.extent 8
dc.format.extent 114-121
dc.language.iso en
dc.relation.ispartofseries JIMD Reports; 58(1)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Ensím
dc.subject Rannsóknir
dc.subject Efnaskipti
dc.subject enzyme assay
dc.subject functional confirmation
dc.subject HPLC
dc.subject MAO-A deficiency
dc.subject variant of uncertain significance
dc.subject Internal Medicine
dc.subject Endocrinology, Diabetes and Metabolism
dc.subject Biochemistry, Genetics and Molecular Biology (miscellaneous)
dc.title Monoamine oxidase A activity in fibroblasts as a functional confirmation of MAOA variants
dc.type /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.1002/jmd2.12194
dc.relation.url http://www.scopus.com/inward/record.url?scp=85102315724&partnerID=8YFLogxK
dc.contributor.department Faculty of Medicine
dc.contributor.department Clinical Laboratory Services, Diagnostics and Blood Bank


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